Summary of included studies

All studies

ExclusiveBF Non_exclusiveBF No_BF sum
Bangladesh 138 178 6 322
Canada 86 48 33 167
Haiti 37 11 0 48
South Africa 86 57 0 143
USA(CA_FL) 150 68 12 230
USA(CA_MA_MO) 38 66 116 220
USA(NC) 12 8 1 21
All studies 547 436 168 1151

All studies for stratified meta-analysis by birth mode

Vaginal C-section sum
Canada 130 37 167
Haiti 42 6 48
USA(CA_FL) 162 65 227
USA(CA_MA_MO) 150 78 228
All studies 484 186 670

Microbiota age

Analysis for microbiota age based on shared genera

microbiota age was predicted based on the Random Forest model using L6 (genus) taxa relative abundance with list of taxa shared by all 7 included studies.

Plot of microbiota age by study all ages

With Generalized additive mixed model (GAMM) fit and 95%CI.

Sample age < 6 months only

Standardized microbiota age and GAMM fit comparison between bf group within each study

Grey color

Meta-analysis for samples in <= 6 months old infants

Meta-analysis models based on adjusted estimate (adjusted for age of infant at sample collection) and standard error from linear mixed effect models.

Change of RM in non-exclusive breastfed (nebf) vs. exclusive breastfed (exbf)

                                           RD            95%-CI %W(fixed)
Thompson et al 2015 ( USA(NC) )        0.8754 [ 0.1366; 1.6142]       1.5
Wood et al 2018 ( South Africa )       0.1214 [-0.2963; 0.5390]       4.7
Pannaraj et al 2017 ( USA(CA_FL) )     0.2665 [ 0.0464; 0.4866]      17.1
Bender et al 2016 ( Haiti )           -0.1769 [-0.8203; 0.4664]       2.0
Subramanian et al 2014 ( Bangladesh )  0.0568 [-0.0605; 0.1741]      60.2
Sordillo et al 2017 ( USA(CA_MA_MO) )  0.7355 [ 0.3600; 1.1109]       5.9
Azad et al 2015 ( Canada )             0.6149 [ 0.3048; 0.9250]       8.6
                                      %W(random)
Thompson et al 2015 ( USA(NC) )              7.3
Wood et al 2018 ( South Africa )            13.4
Pannaraj et al 2017 ( USA(CA_FL) )          18.7
Bender et al 2016 ( Haiti )                  8.7
Subramanian et al 2014 ( Bangladesh )       21.0
Sordillo et al 2017 ( USA(CA_MA_MO) )       14.5
Azad et al 2015 ( Canada )                  16.3

Number of studies combined: k = 7

                         RD           95%-CI    z  p-value
Fixed effect model   0.1913 [0.1003; 0.2823] 4.12 < 0.0001
Random effects model 0.3336 [0.0894; 0.5778] 2.68   0.0074

Quantifying heterogeneity:
tau^2 = 0.0702; H = 2.06 [1.42; 2.98]; I^2 = 76.4% [50.4%; 88.8%]

Test of heterogeneity:
     Q d.f. p-value
 25.40    6  0.0003

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Thompson et al 2015 ( USA(NC) ) 0.0202100021212404
Wood et al 2018 ( South Africa ) 0.569010986228987
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0176451947099079
Bender et al 2016 ( Haiti ) 0.589859305402284
Subramanian et al 2014 ( Bangladesh ) 0.342537683608756
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.000123424504683378
Azad et al 2015 ( Canada ) 0.000101690866421991

Sensitivity analysis

No Haiti data

                                          RD            95%-CI %W(fixed)
Thompson et al 2015 ( USA(NC) )       0.8754 [ 0.1366; 1.6142]       1.5
Wood et al 2018 ( South Africa )      0.1214 [-0.2963; 0.5390]       4.8
Pannaraj et al 2017 ( USA(CA_FL) )    0.2665 [ 0.0464; 0.4866]      17.4
Subramanian et al 2014 ( Bangladesh ) 0.0568 [-0.0605; 0.1741]      61.4
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.7355 [ 0.3600; 1.1109]       6.0
Azad et al 2015 ( Canada )            0.6149 [ 0.3048; 0.9250]       8.8
                                      %W(random)
Thompson et al 2015 ( USA(NC) )              8.1
Wood et al 2018 ( South Africa )            14.8
Pannaraj et al 2017 ( USA(CA_FL) )          20.4
Subramanian et al 2014 ( Bangladesh )       22.9
Sordillo et al 2017 ( USA(CA_MA_MO) )       15.9
Azad et al 2015 ( Canada )                  17.8

Number of studies combined: k = 6

                         RD           95%-CI    z  p-value
Fixed effect model   0.1988 [0.1069; 0.2908] 4.24 < 0.0001
Random effects model 0.3835 [0.1247; 0.6422] 2.90   0.0037

Quantifying heterogeneity:
tau^2 = 0.0726; H = 2.20 [1.49; 3.25]; I^2 = 79.3% [54.7%; 90.5%]

Test of heterogeneity:
     Q d.f. p-value
 24.11    5  0.0002

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Thompson et al 2015 ( USA(NC) ) 0.0202100021212404
Wood et al 2018 ( South Africa ) 0.569010986228987
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0176451947099079
Subramanian et al 2014 ( Bangladesh ) 0.342537683608756
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.000123424504683378
Azad et al 2015 ( Canada ) 0.000101690866421991

No USA(NC) data

                                           RD            95%-CI %W(fixed)
Wood et al 2018 ( South Africa )       0.1214 [-0.2963; 0.5390]       4.8
Pannaraj et al 2017 ( USA(CA_FL) )     0.2665 [ 0.0464; 0.4866]      17.4
Bender et al 2016 ( Haiti )           -0.1769 [-0.8203; 0.4664]       2.0
Subramanian et al 2014 ( Bangladesh )  0.0568 [-0.0605; 0.1741]      61.1
Sordillo et al 2017 ( USA(CA_MA_MO) )  0.7355 [ 0.3600; 1.1109]       6.0
Azad et al 2015 ( Canada )             0.6149 [ 0.3048; 0.9250]       8.7
                                      %W(random)
Wood et al 2018 ( South Africa )            14.3
Pannaraj et al 2017 ( USA(CA_FL) )          20.4
Bender et al 2016 ( Haiti )                  9.1
Subramanian et al 2014 ( Bangladesh )       23.1
Sordillo et al 2017 ( USA(CA_MA_MO) )       15.5
Azad et al 2015 ( Canada )                  17.6

Number of studies combined: k = 6

                         RD           95%-CI    z p-value
Fixed effect model   0.1808 [0.0891; 0.2725] 3.87  0.0001
Random effects model 0.2909 [0.0458; 0.5360] 2.33  0.0200

Quantifying heterogeneity:
tau^2 = 0.0640; H = 2.10 [1.41; 3.13]; I^2 = 77.3% [49.6%; 89.8%]

Test of heterogeneity:
     Q d.f. p-value
 22.05    5  0.0005

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Wood et al 2018 ( South Africa ) 0.569010986228987
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0176451947099079
Bender et al 2016 ( Haiti ) 0.589859305402284
Subramanian et al 2014 ( Bangladesh ) 0.342537683608756
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.000123424504683378
Azad et al 2015 ( Canada ) 0.000101690866421991

No USA(CA_MA_MO) data

                                           RD            95%-CI %W(fixed)
Thompson et al 2015 ( USA(NC) )        0.8754 [ 0.1366; 1.6142]       1.6
Wood et al 2018 ( South Africa )       0.1214 [-0.2963; 0.5390]       5.0
Pannaraj et al 2017 ( USA(CA_FL) )     0.2665 [ 0.0464; 0.4866]      18.2
Bender et al 2016 ( Haiti )           -0.1769 [-0.8203; 0.4664]       2.1
Subramanian et al 2014 ( Bangladesh )  0.0568 [-0.0605; 0.1741]      63.9
Azad et al 2015 ( Canada )             0.6149 [ 0.3048; 0.9250]       9.1
                                      %W(random)
Thompson et al 2015 ( USA(NC) )              7.4
Wood et al 2018 ( South Africa )            15.0
Pannaraj et al 2017 ( USA(CA_FL) )          22.8
Bender et al 2016 ( Haiti )                  9.0
Subramanian et al 2014 ( Bangladesh )       26.7
Azad et al 2015 ( Canada )                  19.0

Number of studies combined: k = 6

                         RD           95%-CI    z p-value
Fixed effect model   0.1574 [0.0636; 0.2512] 3.29  0.0010
Random effects model 0.2602 [0.0267; 0.4936] 2.18  0.0290

Quantifying heterogeneity:
tau^2 = 0.0495; H = 1.83 [1.20; 2.80]; I^2 = 70.3% [30.5%; 87.3%]

Test of heterogeneity:
     Q d.f. p-value
 16.83    5  0.0048

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Thompson et al 2015 ( USA(NC) ) 0.0202100021212404
Wood et al 2018 ( South Africa ) 0.569010986228987
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0176451947099079
Bender et al 2016 ( Haiti ) 0.589859305402284
Subramanian et al 2014 ( Bangladesh ) 0.342537683608756
Azad et al 2015 ( Canada ) 0.000101690866421991

Stratify by birth mode (not standardized)

Vaginal

                                         RD            95%-CI %W(fixed)
Azad et al 2015 (Canada)             2.0223 [ 1.0746; 2.9701]      23.9
Bender et al 2016 (Haiti)           -0.5119 [-2.7851; 1.7614]       4.1
Pannaraj et al 2017 (USA(CA_FL))     0.5934 [-0.0958; 1.2826]      45.1
Sordillo et al 2017 (USA(CA_MA_MO))  1.5749 [ 0.6821; 2.4677]      26.9
                                    %W(random)
Azad et al 2015 (Canada)                  27.7
Bender et al 2016 (Haiti)                 10.8
Pannaraj et al 2017 (USA(CA_FL))          32.8
Sordillo et al 2017 (USA(CA_MA_MO))       28.8

Number of studies combined: k = 4

                         RD           95%-CI    z  p-value
Fixed effect model   1.1523 [0.6894; 1.6152] 4.88 < 0.0001
Random effects model 1.1519 [0.2829; 2.0209] 2.60   0.0094

Quantifying heterogeneity:
tau^2 = 0.4763; H = 1.70 [1.00; 2.92]; I^2 = 65.4% [0.0%; 88.2%]

Test of heterogeneity:
    Q d.f. p-value
 8.68    3  0.0338

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Azad et al 2015 (Canada) 2.88635033937751e-05
Bender et al 2016 (Haiti) 0.658981004403214
Pannaraj et al 2017 (USA(CA_FL)) 0.0914811823311381
Sordillo et al 2017 (USA(CA_MA_MO)) 0.000545678208685348

C-section

                                         RD            95%-CI %W(fixed)
Azad et al 2015 (Canada)             0.6820 [-1.3391; 2.7031]      14.4
Bender et al 2016 (Haiti)           -0.3508 [-4.3974; 3.6958]       3.6
Pannaraj et al 2017 (USA(CA_FL))     0.7880 [-0.2996; 1.8755]      49.7
Sordillo et al 2017 (USA(CA_MA_MO))  1.1977 [-0.1522; 2.5476]      32.3
                                    %W(random)
Azad et al 2015 (Canada)                  14.4
Bender et al 2016 (Haiti)                  3.6
Pannaraj et al 2017 (USA(CA_FL))          49.7
Sordillo et al 2017 (USA(CA_MA_MO))       32.3

Number of studies combined: k = 4

                         RD           95%-CI    z p-value
Fixed effect model   0.8641 [0.0971; 1.6310] 2.21  0.0272
Random effects model 0.8641 [0.0971; 1.6310] 2.21  0.0272

Quantifying heterogeneity:
tau^2 = 0; H = 1.00 [1.00; 1.17]; I^2 = 0.0% [0.0%; 27.2%]

Test of heterogeneity:
    Q d.f. p-value
 0.63    3  0.8893

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Azad et al 2015 (Canada) 0.508396867999409
Bender et al 2016 (Haiti) 0.865079808120753
Pannaraj et al 2017 (USA(CA_FL)) 0.155598040795797
Sordillo et al 2017 (USA(CA_MA_MO)) 0.0820319111581724

Trend of microbiota age in exclusive breastfed (exbf), non-exclusive breastfed (nebf) and no bf

                                        RD            95%-CI %W(fixed)
Subramanian et al 2014 (Bangladesh) 0.0308 [-0.0757; 0.1372]      44.1
Azad et al 2015 (Canada)            0.5818 [ 0.4102; 0.7534]      17.0
Pannaraj et al 2017 (USA(CA_FL))    0.3161 [ 0.1504; 0.4819]      18.2
Sordillo et al 2017 (USA(CA_MA_MO)) 0.5214 [ 0.3626; 0.6802]      19.8
Thompson et al 2015 (USA(NC))       0.2911 [-0.4807; 1.0628]       0.8
                                    %W(random)
Subramanian et al 2014 (Bangladesh)       24.0
Azad et al 2015 (Canada)                  22.6
Pannaraj et al 2017 (USA(CA_FL))          22.7
Sordillo et al 2017 (USA(CA_MA_MO))       22.9
Thompson et al 2015 (USA(NC))              7.8

Number of studies combined: k = 5

                         RD           95%-CI    z  p-value
Fixed effect model   0.2758 [0.2051; 0.3465] 7.64 < 0.0001
Random effects model 0.3526 [0.0926; 0.6125] 2.66   0.0079

Quantifying heterogeneity:
tau^2 = 0.0703; H = 3.24 [2.28; 4.61]; I^2 = 90.5% [80.7%; 95.3%]

Test of heterogeneity:
     Q d.f.  p-value
 41.99    4 < 0.0001

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 (Bangladesh) 0.570837554151296
Azad et al 2015 (Canada) 2.9999698377109e-11
Pannaraj et al 2017 (USA(CA_FL)) 0.000185565976276297
Sordillo et al 2017 (USA(CA_MA_MO)) 1.24192582145007e-10
Thompson et al 2015 (USA(NC)) 0.459754398037424

Exploratory analysis for effect of duration of exbf, formula and solid intro

With GAMM fit and 95%CI.

Subramanian (Bangladesh) data

Number of infants by duration of bf in the test set


<=2 months  >2 months 
        26         13 

Number of samples by duration of bf in the test set


<=2 months  >2 months 
       483        252 

Number of samples by duration of bf in the test set (>6 months only)


<=2 months  >2 months 
       305        176 

Duration (month) of exbf

Grey

Test for age > 6 months and <15months GAM part

Estimate Std. Error t value Pr(>|t|)
(Intercept) 11.516456 0.4287802 26.858644 0.0000000
month.exbf2>2 months -1.634246 0.7401967 -2.207854 0.0280084
edf Ref.df F p-value
s(age.sample):month.exbf2<=2 months 1.000001 1.000001 120.79393 0
s(age.sample):month.exbf2>2 months 1.000000 1.000000 60.88972 0

LME part

Value Std.Error DF t-value p-value
X(Intercept) 11.516456 0.4302022 264 26.769865 0.0000000
Xmonth.exbf2>2 months -1.634246 0.7426508 37 -2.200557 0.0340874
Xs(age.sample):month.exbf2<=2 monthsFx1 2.352653 0.2147700 264 10.954291 0.0000000
Xs(age.sample):month.exbf2>2 monthsFx1 2.231823 0.2869630 264 7.777391 0.0000000

Performance of the Random Forest model to estimate microbiota age

Evaluated on the training and test set of Subramanian (Bangladesh) data.

List of shared taxa and their relative importance

genera importance importance.percent
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__blautia 3264.30 27.17
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__ 1905.28 15.86
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__prevotellaceae.g__prevotella 935.61 7.79
k__bacteria.p__firmicutes.c__clostridia.oclostridiales.f.g__ 903.01 7.52
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae.g__staphylococcus 693.06 5.77
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__dialister 465.34 3.87
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__lactobacillaceae.g__lactobacillus 430.94 3.59
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pasteurellales.f__pasteurellaceae.g__haemophilus 412.80 3.44
k__bacteria.p__actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium 399.63 3.33
k__bacteria.p__actinobacteria.c__actinobacteria.o__actinomycetales.f__actinomycetaceae.g__actinomyces 326.51 2.72
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__dorea 232.91 1.94
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__enterococcaceae.g__enterococcus 211.03 1.76
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__coprococcus 184.24 1.53
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae.g__streptococcus 180.88 1.51
k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__collinsella 157.80 1.31
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__veillonella 157.13 1.31
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae.g__clostridium 132.33 1.10
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__ruminococcaceae.g__oscillospira 127.32 1.06
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 125.65 1.05
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pseudomonadales.f__pseudomonadaceae.g__pseudomonas 117.28 0.98
k__bacteria.p__actinobacteria.c__actinobacteria.o__actinomycetales.f__micrococcaceae.g__rothia 105.70 0.88
k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__ 100.02 0.83
k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__atopobium 66.97 0.56
k__bacteria.p__proteobacteria.c__betaproteobacteria.o__neisseriales.f__neisseriaceae.g__neisseria 59.31 0.49
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__porphyromonadaceae.g__parabacteroides 54.37 0.45
k__bacteria.p__proteobacteria.c__betaproteobacteria.o__burkholderiales.f__alcaligenaceae.g__sutterella 53.38 0.44
k__bacteria.p__fusobacteria.c__fusobacteriia.o__fusobacteriales.f__fusobacteriaceae.g__fusobacterium 52.32 0.44
k__bacteria.p__firmicutes.c__bacilli.o__gemellales.f__gemellaceae.g__ 51.81 0.43
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae.g__lactococcus 44.64 0.37
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__rikenellaceae.g__ 32.71 0.27
k__bacteria.p__cyanobacteria.c__chloroplast.ostreptophyta.f.g__ 10.73 0.09
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__acidaminococcus 7.19 0.06
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__roseburia 6.31 0.05
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__carnobacteriaceae.g__granulicatella 4.29 0.04
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__paenibacillaceae.g__paenibacillus 0.14 0.00
k__bacteria.p__proteobacteria.c__alphaproteobacteria.o__sphingomonadales.f__sphingomonadaceae.g__sphingomonas 0.11 0.00

Alpha diversity indexes

Plots of alpha diversity by study by age

With GAMM fit and 95%CI.

Samples <= 6 months only

GAMM fit comparison between bf group within each study

Samples <=6 months only

Exploration by duration of exclusive bf

Subramanian (Bangladesh) data only.

Exclusive bf duration

Shannon index.

Meta-analysis

For samples <=6 months old only.

Change in non-exbf vs. exbf

Chao1

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.0677 [-0.0136; 0.1491]      79.0
Azad et al 2015 ( Canada )            0.3752 [ 0.0596; 0.6908]       5.3
Bender et al 2016 ( Haiti )           0.4922 [-0.3266; 1.3110]       0.8
Wood et al 2018 ( South Africa )      0.5113 [ 0.0923; 0.9303]       3.0
Pannaraj et al 2017 ( USA(CA_FL) )    0.1201 [-0.1362; 0.3764]       8.0
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.6457 [ 0.2430; 1.0485]       3.2
Thompson et al 2015 ( USA(NC) )       0.4111 [-0.4054; 1.2277]       0.8
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       28.0
Azad et al 2015 ( Canada )                  16.8
Bender et al 2016 ( Haiti )                  4.9
Wood et al 2018 ( South Africa )            12.6
Pannaraj et al 2017 ( USA(CA_FL) )          19.6
Sordillo et al 2017 ( USA(CA_MA_MO) )       13.2
Thompson et al 2015 ( USA(NC) )              4.9

Number of studies combined: k = 7

                         RD           95%-CI    z p-value
Fixed effect model   0.1259 [0.0536; 0.1982] 3.41  0.0006
Random effects model 0.2995 [0.1020; 0.4969] 2.97  0.0030

Quantifying heterogeneity:
tau^2 = 0.0346; H = 1.59 [1.05; 2.41]; I^2 = 60.7% [9.9%; 82.8%]

Test of heterogeneity:
     Q d.f. p-value
 15.25    6  0.0184

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.102847325927163
Azad et al 2015 ( Canada ) 0.01980051110656
Bender et al 2016 ( Haiti ) 0.238756122389415
Wood et al 2018 ( South Africa ) 0.0167677830041401
Pannaraj et al 2017 ( USA(CA_FL) ) 0.358399385859461
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.00167635766494574
Thompson et al 2015 ( USA(NC) ) 0.32371285335117

Observed_species

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.0673 [-0.0127; 0.1473]      77.1
Azad et al 2015 ( Canada )            0.3721 [ 0.0590; 0.6852]       5.0
Bender et al 2016 ( Haiti )           0.4601 [-0.3413; 1.2616]       0.8
Wood et al 2018 ( South Africa )      0.4996 [ 0.0848; 0.9143]       2.9
Pannaraj et al 2017 ( USA(CA_FL) )    0.1447 [-0.0763; 0.3657]      10.1
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.6461 [ 0.2454; 1.0467]       3.1
Thompson et al 2015 ( USA(NC) )       0.3555 [-0.3448; 1.0557]       1.0
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       28.2
Azad et al 2015 ( Canada )                  16.1
Bender et al 2016 ( Haiti )                  4.5
Wood et al 2018 ( South Africa )            12.0
Pannaraj et al 2017 ( USA(CA_FL) )          21.0
Sordillo et al 2017 ( USA(CA_MA_MO) )       12.5
Thompson et al 2015 ( USA(NC) )              5.7

Number of studies combined: k = 7

                         RD           95%-CI    z p-value
Fixed effect model   0.1266 [0.0564; 0.1969] 3.53  0.0004
Random effects model 0.2909 [0.1053; 0.4765] 3.07  0.0021

Quantifying heterogeneity:
tau^2 = 0.0301; H = 1.59 [1.05; 2.41]; I^2 = 60.4% [9.1%; 82.7%]

Test of heterogeneity:
     Q d.f. p-value
 15.14    6  0.0192

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.0990100956520888
Azad et al 2015 ( Canada ) 0.019839103185688
Bender et al 2016 ( Haiti ) 0.260501865374435
Wood et al 2018 ( South Africa ) 0.0182288177251842
Pannaraj et al 2017 ( USA(CA_FL) ) 0.19952096913775
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.00157427402976728
Thompson et al 2015 ( USA(NC) ) 0.319751771051308

Pd_whole_tree

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.0953 [ 0.0196; 0.1710]      80.5
Azad et al 2015 ( Canada )            0.2877 [-0.0327; 0.6082]       4.5
Bender et al 2016 ( Haiti )           0.3082 [-0.3766; 0.9931]       1.0
Wood et al 2018 ( South Africa )      0.4724 [ 0.0489; 0.8958]       2.6
Pannaraj et al 2017 ( USA(CA_FL) )    0.2168 [ 0.0121; 0.4215]      11.0
Thompson et al 2015 ( USA(NC) )       0.7261 [-0.2385; 1.6906]       0.5
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       52.8
Azad et al 2015 ( Canada )                  12.0
Bender et al 2016 ( Haiti )                  3.1
Wood et al 2018 ( South Africa )             7.4
Pannaraj et al 2017 ( USA(CA_FL) )          23.2
Thompson et al 2015 ( USA(NC) )              1.6

Number of studies combined: k = 6

                         RD           95%-CI    z p-value
Fixed effect model   0.1322 [0.0643; 0.2001] 3.82  0.0001
Random effects model 0.1910 [0.0685; 0.3134] 3.06  0.0022

Quantifying heterogeneity:
tau^2 = 0.0059; H = 1.15 [1.00; 1.78]; I^2 = 25.0% [0.0%; 68.4%]

Test of heterogeneity:
    Q d.f. p-value
 6.66    5  0.2469

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.0136266394489582
Azad et al 2015 ( Canada ) 0.0784131649118116
Bender et al 2016 ( Haiti ) 0.377692577417145
Wood et al 2018 ( South Africa ) 0.0288048675369895
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0379096968161372
Thompson et al 2015 ( USA(NC) ) 0.140133230873501

Shannon

                                           RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh )  0.2592 [ 0.1185; 0.3999]      57.3
Azad et al 2015 ( Canada )             0.3262 [ 0.0159; 0.6365]      11.8
Bender et al 2016 ( Haiti )           -0.1146 [-0.7954; 0.5662]       2.4
Wood et al 2018 ( South Africa )       0.3071 [-0.1311; 0.7452]       5.9
Pannaraj et al 2017 ( USA(CA_FL) )     0.3732 [ 0.0808; 0.6657]      13.3
Sordillo et al 2017 ( USA(CA_MA_MO) )  0.7684 [ 0.3821; 1.1546]       7.6
Thompson et al 2015 ( USA(NC) )        0.3001 [-0.5308; 1.1310]       1.6
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       40.5
Azad et al 2015 ( Canada )                  15.7
Bender et al 2016 ( Haiti )                  4.0
Wood et al 2018 ( South Africa )             8.9
Pannaraj et al 2017 ( USA(CA_FL) )          17.2
Sordillo et al 2017 ( USA(CA_MA_MO) )       11.0
Thompson et al 2015 ( USA(NC) )              2.7

Number of studies combined: k = 7

                         RD           95%-CI    z  p-value
Fixed effect model   0.3153 [0.2088; 0.4219] 5.80 < 0.0001
Random effects model 0.3359 [0.1959; 0.4759] 4.70 < 0.0001

Quantifying heterogeneity:
tau^2 = 0.0074; H = 1.12 [1.00; 1.67]; I^2 = 20.9% [0.0%; 64.3%]

Test of heterogeneity:
    Q d.f. p-value
 7.59    6  0.2700

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.000305463231694058
Azad et al 2015 ( Canada ) 0.0393559233405728
Bender et al 2016 ( Haiti ) 0.74142212926805
Wood et al 2018 ( South Africa ) 0.169568310346119
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0123688713005407
Sordillo et al 2017 ( USA(CA_MA_MO) ) 9.65594918082499e-05
Thompson et al 2015 ( USA(NC) ) 0.479014124949741

Sensitivity analysis Change in non-exbf vs. exbf

Show the results of Shannon indexes only.

No Haiti data

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.2592 [ 0.1185; 0.3999]      58.8
Azad et al 2015 ( Canada )            0.3262 [ 0.0159; 0.6365]      12.1
Wood et al 2018 ( South Africa )      0.3071 [-0.1311; 0.7452]       6.1
Pannaraj et al 2017 ( USA(CA_FL) )    0.3732 [ 0.0808; 0.6657]      13.6
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.7684 [ 0.3821; 1.1546]       7.8
Thompson et al 2015 ( USA(NC) )       0.3001 [-0.5308; 1.1310]       1.7
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       45.8
Azad et al 2015 ( Canada )                  15.5
Wood et al 2018 ( South Africa )             8.5
Pannaraj et al 2017 ( USA(CA_FL) )          17.1
Sordillo et al 2017 ( USA(CA_MA_MO) )       10.6
Thompson et al 2015 ( USA(NC) )              2.5

Number of studies combined: k = 6

                         RD           95%-CI    z  p-value
Fixed effect model   0.3261 [0.2183; 0.4340] 5.93 < 0.0001
Random effects model 0.3483 [0.2145; 0.4821] 5.10 < 0.0001

Quantifying heterogeneity:
tau^2 = 0.0050; H = 1.10 [1.00; 1.61]; I^2 = 16.9% [0.0%; 61.6%]

Test of heterogeneity:
    Q d.f. p-value
 6.02    5  0.3047

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.000305463231694058
Azad et al 2015 ( Canada ) 0.0393559233405728
Wood et al 2018 ( South Africa ) 0.169568310346119
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0123688713005407
Sordillo et al 2017 ( USA(CA_MA_MO) ) 9.65594918082499e-05
Thompson et al 2015 ( USA(NC) ) 0.479014124949741

No UNC data

                                           RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh )  0.2592 [ 0.1185; 0.3999]      58.3
Azad et al 2015 ( Canada )             0.3262 [ 0.0159; 0.6365]      12.0
Bender et al 2016 ( Haiti )           -0.1146 [-0.7954; 0.5662]       2.5
Wood et al 2018 ( South Africa )       0.3071 [-0.1311; 0.7452]       6.0
Pannaraj et al 2017 ( USA(CA_FL) )     0.3732 [ 0.0808; 0.6657]      13.5
Sordillo et al 2017 ( USA(CA_MA_MO) )  0.7684 [ 0.3821; 1.1546]       7.7
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       36.5
Azad et al 2015 ( Canada )                  17.2
Bender et al 2016 ( Haiti )                  4.9
Wood et al 2018 ( South Africa )            10.3
Pannaraj et al 2017 ( USA(CA_FL) )          18.6
Sordillo et al 2017 ( USA(CA_MA_MO) )       12.6

Number of studies combined: k = 6

                         RD           95%-CI    z  p-value
Fixed effect model   0.3156 [0.2082; 0.4230] 5.76 < 0.0001
Random effects model 0.3427 [0.1851; 0.5004] 4.26 < 0.0001

Quantifying heterogeneity:
tau^2 = 0.0126; H = 1.23 [1.00; 1.94]; I^2 = 34.1% [0.0%; 73.5%]

Test of heterogeneity:
    Q d.f. p-value
 7.58    5  0.1807

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.000305463231694058
Azad et al 2015 ( Canada ) 0.0393559233405728
Bender et al 2016 ( Haiti ) 0.74142212926805
Wood et al 2018 ( South Africa ) 0.169568310346119
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0123688713005407
Sordillo et al 2017 ( USA(CA_MA_MO) ) 9.65594918082499e-05

No USA(CA_MA_MO) data

                                           RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh )  0.2592 [ 0.1185; 0.3999]      62.0
Azad et al 2015 ( Canada )             0.3262 [ 0.0159; 0.6365]      12.8
Bender et al 2016 ( Haiti )           -0.1146 [-0.7954; 0.5662]       2.7
Wood et al 2018 ( South Africa )       0.3071 [-0.1311; 0.7452]       6.4
Pannaraj et al 2017 ( USA(CA_FL) )     0.3732 [ 0.0808; 0.6657]      14.4
Thompson et al 2015 ( USA(NC) )        0.3001 [-0.5308; 1.1310]       1.8
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       62.0
Azad et al 2015 ( Canada )                  12.8
Bender et al 2016 ( Haiti )                  2.7
Wood et al 2018 ( South Africa )             6.4
Pannaraj et al 2017 ( USA(CA_FL) )          14.4
Thompson et al 2015 ( USA(NC) )              1.8

Number of studies combined: k = 6

                         RD           95%-CI    z  p-value
Fixed effect model   0.2780 [0.1672; 0.3889] 4.92 < 0.0001
Random effects model 0.2780 [0.1672; 0.3889] 4.92 < 0.0001

Quantifying heterogeneity:
tau^2 = 0; H = 1.00 [1.00; 1.21]; I^2 = 0.0% [0.0%; 32.0%]

Test of heterogeneity:
    Q d.f. p-value
 1.87    5  0.8674

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.000305463231694058
Azad et al 2015 ( Canada ) 0.0393559233405728
Bender et al 2016 ( Haiti ) 0.74142212926805
Wood et al 2018 ( South Africa ) 0.169568310346119
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0123688713005407
Thompson et al 2015 ( USA(NC) ) 0.479014124949741

Stratify by birth mode for Change in non-exbf vs. exbf (not standardized)

Show results of Shannon index only.

Vaginal

                                         RD            95%-CI %W(fixed)
 Azad et al 2015 (Canada)            0.1424 [-0.0984; 0.3832]      40.8
Bender et al 2016 (Haiti)           -0.2018 [-0.9752; 0.5715]       4.0
Pannaraj et al 2017 (USA(CA_FL))     0.3734 [ 0.1294; 0.6174]      39.7
Sordillo et al 2017 (USA(CA_MA_MO))  0.4321 [ 0.0420; 0.8223]      15.5
                                    %W(random)
 Azad et al 2015 (Canada)                 38.3
Bender et al 2016 (Haiti)                  5.4
Pannaraj et al 2017 (USA(CA_FL))          37.6
Sordillo et al 2017 (USA(CA_MA_MO))       18.6

Number of studies combined: k = 4

                         RD           95%-CI    z p-value
Fixed effect model   0.2656 [0.1118; 0.4194] 3.38  0.0007
Random effects model 0.2647 [0.0798; 0.4495] 2.81  0.0050

Quantifying heterogeneity:
tau^2 = 0.0081; H = 1.13 [1.00; 2.90]; I^2 = 22.3% [0.0%; 88.1%]

Test of heterogeneity:
    Q d.f. p-value
 3.86    3  0.2771

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Azad et al 2015 (Canada) 0.246532761397953
Bender et al 2016 (Haiti) 0.608996225108868
Pannaraj et al 2017 (USA(CA_FL)) 0.00270151112577258
Sordillo et al 2017 (USA(CA_MA_MO)) 0.0299341350698865

C-section

                                         RD            95%-CI %W(fixed)
 Azad et al 2015 (Canada)            0.4873 [ 0.0230; 0.9515]      40.3
Pannaraj et al 2017 (USA(CA_FL))    -0.0737 [-0.5869; 0.4395]      33.0
Sordillo et al 2017 (USA(CA_MA_MO))  1.0833 [ 0.5127; 1.6540]      26.7
                                    %W(random)
 Azad et al 2015 (Canada)                 34.9
Pannaraj et al 2017 (USA(CA_FL))          33.4
Sordillo et al 2017 (USA(CA_MA_MO))       31.7

Number of studies combined: k = 3

                         RD            95%-CI    z p-value
Fixed effect model   0.4612 [ 0.1665; 0.7560] 3.07  0.0022
Random effects model 0.4888 [-0.1327; 1.1103] 1.54  0.1232

Quantifying heterogeneity:
tau^2 = 0.2323; H = 2.09 [1.16; 3.77]; I^2 = 77.1% [25.6%; 93.0%]

Test of heterogeneity:
    Q d.f. p-value
 8.75    2  0.0126

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Azad et al 2015 (Canada) 0.0396622679428872
Pannaraj et al 2017 (USA(CA_FL)) 0.778417002121859
Sordillo et al 2017 (USA(CA_MA_MO)) 0.000198560001433614

Put meta-analysis results (random models) of all indexes together

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
shannon 0.3359260 0.0714283 0.1959290 0.4759229 4.702980 0.0000026 0.0000103
observed_species 0.2908894 0.0946918 0.1052969 0.4764819 3.071960 0.0021266 0.0029552
pd_whole_tree 0.1909514 0.0624970 0.0684595 0.3134432 3.055369 0.0022478 0.0029552
chao1 0.2994547 0.1007464 0.1019953 0.4969141 2.972360 0.0029552 0.0029552

Trend effect in exbf, non-exbf, no bf

Chao1

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.0550 [-0.0189; 0.1289]      65.2
Azad et al 2015 ( Canada )            0.5725 [ 0.3986; 0.7464]      11.8
Bender et al 2016 ( Haiti )               NA                         0.0
Wood et al 2018 ( South Africa )          NA                         0.0
Pannaraj et al 2017 ( USA(CA_FL) )    0.1302 [-0.0599; 0.3202]       9.9
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.4245 [ 0.2553; 0.5937]      12.4
Thompson et al 2015 ( USA(NC) )       0.4233 [-0.2687; 1.1153]       0.7
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       24.7
Azad et al 2015 ( Canada )                  22.4
Bender et al 2016 ( Haiti )                  0.0
Wood et al 2018 ( South Africa )             0.0
Pannaraj et al 2017 ( USA(CA_FL) )          21.9
Sordillo et al 2017 ( USA(CA_MA_MO) )       22.6
Thompson et al 2015 ( USA(NC) )              8.3

Number of studies combined: k = 5

                         RD           95%-CI    z  p-value
Fixed effect model   0.1720 [0.1123; 0.2316] 5.65 < 0.0001
Random effects model 0.3016 [0.0580; 0.5451] 2.43   0.0152

Quantifying heterogeneity:
tau^2 = 0.0610; H = 3.13 [2.19; 4.49]; I^2 = 89.8% [79.1%; 95.0%]

Test of heterogeneity:
     Q d.f.  p-value
 39.26    4 < 0.0001

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.144460866036347
Azad et al 2015 ( Canada ) 1.0991009354299e-10
Bender et al 2016 ( Haiti ) NA
Wood et al 2018 ( South Africa ) NA
Pannaraj et al 2017 ( USA(CA_FL) ) 0.179455833167877
Sordillo et al 2017 ( USA(CA_MA_MO) ) 8.77670396356771e-07
Thompson et al 2015 ( USA(NC) ) 0.230600549600578

Observed_species

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.0603 [-0.0124; 0.1329]      63.5
Azad et al 2015 ( Canada )            0.5895 [ 0.4168; 0.7623]      11.2
Bender et al 2016 ( Haiti )               NA                         0.0
Wood et al 2018 ( South Africa )          NA                         0.0
Pannaraj et al 2017 ( USA(CA_FL) )    0.1163 [-0.0479; 0.2806]      12.4
Sordillo et al 2017 ( USA(CA_MA_MO) ) 0.4610 [ 0.2928; 0.6291]      11.9
Thompson et al 2015 ( USA(NC) )       0.3661 [-0.2275; 0.9598]       1.0
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       24.1
Azad et al 2015 ( Canada )                  21.9
Bender et al 2016 ( Haiti )                  0.0
Wood et al 2018 ( South Africa )             0.0
Pannaraj et al 2017 ( USA(CA_FL) )          22.1
Sordillo et al 2017 ( USA(CA_MA_MO) )       22.0
Thompson et al 2015 ( USA(NC) )             10.0

Number of studies combined: k = 5

                         RD           95%-CI    z  p-value
Fixed effect model   0.1772 [0.1192; 0.2351] 6.00 < 0.0001
Random effects model 0.3070 [0.0641; 0.5500] 2.48   0.0133

Quantifying heterogeneity:
tau^2 = 0.0625; H = 3.30 [2.33; 4.69]; I^2 = 90.8% [81.6%; 95.4%]

Test of heterogeneity:
     Q d.f.  p-value
 43.68    4 < 0.0001

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.104033167825551
Azad et al 2015 ( Canada ) 2.26960893212611e-11
Bender et al 2016 ( Haiti ) NA
Wood et al 2018 ( South Africa ) NA
Pannaraj et al 2017 ( USA(CA_FL) ) 0.165000455562882
Sordillo et al 2017 ( USA(CA_MA_MO) ) 7.73447284594136e-08
Thompson et al 2015 ( USA(NC) ) 0.226684364502839

Pd_whole_tree

                                          RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh ) 0.0646 [-0.0047; 0.1338]      72.9
Azad et al 2015 ( Canada )            0.5311 [ 0.3540; 0.7082]      11.2
Bender et al 2016 ( Haiti )               NA                         0.0
Wood et al 2018 ( South Africa )          NA                         0.0
Pannaraj et al 2017 ( USA(CA_FL) )    0.2032 [ 0.0523; 0.3541]      15.4
Thompson et al 2015 ( USA(NC) )       0.8566 [ 0.0509; 1.6623]       0.5
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       32.9
Azad et al 2015 ( Canada )                  29.1
Bender et al 2016 ( Haiti )                  0.0
Wood et al 2018 ( South Africa )             0.0
Pannaraj et al 2017 ( USA(CA_FL) )          30.2
Thompson et al 2015 ( USA(NC) )              7.8

Number of studies combined: k = 4

                         RD           95%-CI    z  p-value
Fixed effect model   0.1422 [0.0830; 0.2013] 4.71 < 0.0001
Random effects model 0.3037 [0.0475; 0.5598] 2.32   0.0202

Quantifying heterogeneity:
tau^2 = 0.0506; H = 3.00 [1.97; 4.57]; I^2 = 88.9% [74.2%; 95.2%]

Test of heterogeneity:
     Q d.f.  p-value
 26.99    3 < 0.0001

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.0676383461236607
Azad et al 2015 ( Canada ) 4.17049539317814e-09
Bender et al 2016 ( Haiti ) NA
Wood et al 2018 ( South Africa ) NA
Pannaraj et al 2017 ( USA(CA_FL) ) 0.00831447939658577
Thompson et al 2015 ( USA(NC) ) 0.0371791605971582

Shannon

                                           RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh )  0.2131 [ 0.0843; 0.3420]      39.0
Azad et al 2015 ( Canada )             0.5872 [ 0.4153; 0.7590]      21.9
Pannaraj et al 2017 ( USA(CA_FL) )     0.2570 [ 0.0375; 0.4765]      13.5
Sordillo et al 2017 ( USA(CA_MA_MO) )  0.5660 [ 0.4038; 0.7282]      24.6
Thompson et al 2015 ( USA(NC) )       -0.0180 [-0.8408; 0.8049]       1.0
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       25.8
Azad et al 2015 ( Canada )                  23.8
Pannaraj et al 2017 ( USA(CA_FL) )          21.4
Sordillo et al 2017 ( USA(CA_MA_MO) )       24.2
Thompson et al 2015 ( USA(NC) )              4.8

Number of studies combined: k = 5

                         RD           95%-CI    z  p-value
Fixed effect model   0.3858 [0.3053; 0.4663] 9.39 < 0.0001
Random effects model 0.3857 [0.1872; 0.5843] 3.81   0.0001

Quantifying heterogeneity:
tau^2 = 0.0355; H = 2.19 [1.42; 3.37]; I^2 = 79.1% [50.4%; 91.2%]

Test of heterogeneity:
     Q d.f. p-value
 19.16    4  0.0007

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.00119013497616748
Azad et al 2015 ( Canada ) 2.14964602978342e-11
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0217486284946625
Sordillo et al 2017 ( USA(CA_MA_MO) ) 7.9318409863511e-12
Thompson et al 2015 ( USA(NC) ) 0.965887658685873

Put meta-analysis results (random models) of all indexes together

estimate.conbf se.conbf ll.conbf ul.conbf z.conbf p.conbf p.adjust.conbf
shannon 0.3857475 0.1012964 0.1872101 0.5842849 3.808105 0.0001400 0.0005601
observed_species 0.3070476 0.1239712 0.0640686 0.5500267 2.476766 0.0132579 0.0201585
pd_whole_tree 0.3036608 0.1306976 0.0474982 0.5598233 2.323384 0.0201585 0.0201585
chao1 0.3015700 0.1242513 0.0580420 0.5450980 2.427098 0.0152201 0.0201585

Meta-analysis of taxa relative abundance

Results of 7 studies.

For samples <= 6 months old only in all studies (note for USA(NC) study: GAMLSS BEZI with random subject effect could not run on very small sample size=> did not include subject random effect). Results of random meta-analysis models for taxa available in at least >50% of studies based on adjusted estimates and standard errors from GAMLSS models with zero-inflated beta family adjusted for infant age at sample collection.

Meta-analysis of Change in non-exbf vs. exbf adjusted for age

GAMLSS models with zero-inflated beta family

Phylum (l2)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes 0.25 0.0684909 0.11 0.38 3.616776 3e-04 0.0018
k__bacteria.p__bacteroidetes 0.21 0.0756683 0.06 0.36 2.748422 6e-03 0.0180

Nice plot

Order (l4)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales 0.30 0.0904382 0.12 0.48 3.334046 0.0009 0.0106
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.21 0.0757620 0.06 0.36 2.772512 0.0056 0.0369
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.20 0.0896354 0.02 0.38 2.236847 0.0253 0.1170

Nice plot

Family (l5)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae 0.23 0.0856673 0.06 0.40 2.698284 0.0070 0.0757
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae 0.21 0.0807013 0.05 0.37 2.611789 0.0090 0.0856
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.20 0.0896354 0.02 0.38 2.236847 0.0253 0.1748
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae 0.17 0.0841374 0.00 0.33 1.963771 0.0496 0.3087

Nice plot

Genus (l6)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.39 0.1237182 0.15 0.64 3.173387 0.0015 0.0561
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__megasphaera 0.40 0.1416041 0.12 0.68 2.825361 0.0047 0.1115
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 0.21 0.0807013 0.05 0.37 2.611789 0.0090 0.1220
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__clostridium 0.35 0.1505929 0.05 0.64 2.293839 0.0218 0.2513
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__veillonella 0.21 0.1033136 0.01 0.42 2.068028 0.0386 0.3598

Nice plot

Sensitivity meta-analysis of Change in non-exbf vs. exbf adjusted for age

No UNC data

l2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes 0.25 0.0691970 0.11 0.38 3.568106 0.0004 0.0025
k__bacteria.p__bacteroidetes 0.19 0.0763734 0.04 0.34 2.530586 0.0114 0.0399

l4

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales 0.28 0.0889258 0.11 0.46 3.170900 0.0015 0.0233
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.20 0.0764693 0.05 0.35 2.554669 0.0106 0.0873
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.20 0.0908867 0.02 0.38 2.190489 0.0285 0.1638

l5

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae 0.19 0.0815355 0.03 0.35 2.388972 0.0169 0.2092
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae 0.22 0.0940439 0.04 0.41 2.373553 0.0176 0.2092
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.20 0.0908867 0.02 0.38 2.190489 0.0285 0.2460

l6

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.40 0.1275892 0.15 0.65 3.111909 0.0019 0.0888
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__megasphaera 0.40 0.1416041 0.12 0.68 2.825361 0.0047 0.1804
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae.g__ 0.24 0.0943469 0.06 0.43 2.570734 0.0101 0.2417
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 0.19 0.0815355 0.03 0.35 2.388972 0.0169 0.2804
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__clostridium 0.35 0.1505929 0.05 0.64 2.293839 0.0218 0.3203

No Haiti data

l2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes 0.26 0.0699441 0.12 0.40 3.696729 0.0002 0.0013
k__bacteria.p__bacteroidetes 0.21 0.0769990 0.06 0.36 2.776286 0.0055 0.0165

l4

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales 0.32 0.0708228 0.18 0.46 4.515471 0.0000 0.0001
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.22 0.0770481 0.07 0.37 2.857121 0.0043 0.0325
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.18 0.0915095 0.00 0.36 2.010465 0.0444 0.2108

l5

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae 0.21 0.0822865 0.04 0.37 2.504798 0.0123 0.1348
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae 0.21 0.0969374 0.02 0.40 2.126103 0.0335 0.2947
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.18 0.0915095 0.00 0.36 2.010465 0.0444 0.2947
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae 0.17 0.0868412 0.00 0.34 1.996101 0.0459 0.2947

l6

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__megasphaera 0.45 0.1519683 0.15 0.75 2.975441 0.0029 0.1063
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.36 0.1297330 0.11 0.61 2.770714 0.0056 0.1063
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 0.21 0.0822865 0.04 0.37 2.504798 0.0123 0.1862
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__clostridium 0.36 0.1521514 0.06 0.65 2.338328 0.0194 0.2677
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__coprococcus 0.52 0.2401244 0.05 0.99 2.165979 0.0303 0.3840
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae.g__ 0.53 0.2586130 0.03 1.04 2.066443 0.0388 0.3878

No USA(CA_MA_MO) data

l2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__bacteroidetes 0.23 0.0810268 0.07 0.39 2.854058 0.0043 0.0251
k__bacteria.p__firmicutes 0.20 0.0745996 0.05 0.35 2.689210 0.0072 0.0251

l4

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.23 0.0811408 0.07 0.39 2.880970 0.0040 0.0549
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales 0.30 0.1099207 0.08 0.51 2.700967 0.0069 0.0549
k__bacteria.p__actinobacteria.c__actinobacteria.o__actinomycetales -0.16 0.0644216 -0.28 -0.03 -2.418256 0.0156 0.1025
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.21 0.0993562 0.02 0.41 2.130727 0.0331 0.1692
k__bacteria.p__firmicutes.c__bacilli.o__bacillales -0.21 0.1040509 -0.41 -0.01 -2.026511 0.0427 0.1965

l5

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae 0.30 0.0741081 0.15 0.44 4.042869 0.0001 0.0050
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae 0.24 0.0870795 0.07 0.41 2.727563 0.0064 0.0851
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.21 0.0993562 0.02 0.41 2.130727 0.0331 0.2621

l6

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__acidaminococcus 2.06 0.5761745 0.93 3.19 3.582354 0.0003 0.0306
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.41 0.1362642 0.14 0.68 3.023725 0.0025 0.1074
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__megasphaera 0.45 0.1618768 0.14 0.77 2.799657 0.0051 0.1074
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 0.24 0.0870795 0.07 0.41 2.727563 0.0064 0.1074
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__veillonella 0.26 0.1085724 0.05 0.47 2.404864 0.0162 0.2080
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__clostridium 0.35 0.1505929 0.05 0.64 2.293839 0.0218 0.2616
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__coprococcus 0.55 0.2571987 0.04 1.05 2.126889 0.0334 0.3167

Stratified analysis by birth mode for change in non-exbf vs. exbf adjusted for age

Vaginal

l2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__proteobacteria -0.31 0.1017253 -0.51 -0.11 -3.017517 0.0025 0.0178

l4

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales -0.30 0.1074593 -0.51 -0.09 -2.782951 0.0054 0.1158
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.28 0.1232153 0.04 0.52 2.294944 0.0217 0.2337

l5

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae -0.33 0.1174047 -0.56 -0.10 -2.833865 0.0046 0.1157
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae -0.30 0.1074593 -0.51 -0.09 -2.782951 0.0054 0.1157
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae 0.30 0.1105580 0.08 0.52 2.728721 0.0064 0.1157
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__eubacteriaceae 0.80 0.3139899 0.19 1.42 2.562377 0.0104 0.1577
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.28 0.1232153 0.04 0.52 2.294944 0.0217 0.2198

l6

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__acidaminococcus 3.37 0.4300060 2.53 4.21 7.833648 0.0000 0.0000
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae.g__staphylococcus -0.33 0.1174105 -0.56 -0.10 -2.836711 0.0046 0.1176
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__eubacteriaceae.g__pseudoramibacter_eubacterium 0.88 0.3157991 0.26 1.50 2.774622 0.0055 0.1176
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__ 0.32 0.1163513 0.09 0.55 2.733460 0.0063 0.1176
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 0.30 0.1105580 0.08 0.52 2.728721 0.0064 0.1176
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.54 0.2026827 0.14 0.94 2.656820 0.0079 0.1327
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae.g__ -0.29 0.1148106 -0.51 -0.06 -2.493051 0.0127 0.1802
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae.g__ 0.30 0.1238937 0.06 0.55 2.443764 0.0145 0.1921
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pasteurellales.f__pasteurellaceae.g__aggregatibacter 0.57 0.2477375 0.09 1.06 2.309983 0.0209 0.2234
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae.g__lactococcus 0.58 0.2676966 0.06 1.11 2.179940 0.0293 0.2849
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__blautia 0.36 0.1848815 0.00 0.73 1.968416 0.0490 0.4534

C-section

l2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__proteobacteria -0.72 0.1708821 -1.05 -0.38 -4.211478 0 2e-04

l4

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales -0.58 0.2324176 -1.03 -0.12 -2.493087 0.0127 0.1562

l5

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae -0.58 0.2324176 -1.03 -0.12 -2.493087 0.0127 0.2596

l6

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae.g__proteus -0.26 0.0008395 -0.26 -0.26 -307.189026 0.0000 0.0000
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__ruminococcaceae.g__anaerotruncus -2.92 0.7060795 -4.31 -1.54 -4.141797 0.0000 0.0019
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__phascolarctobacterium -1.88 0.8567398 -3.56 -0.20 -2.199114 0.0279 0.6490
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae.g__ -0.52 0.2608359 -1.03 -0.01 -2.003505 0.0451 0.9154

Meta-analysis of Trend in exbf, non-exbf and no bf adjusted for age

Phylum (l2)

Significant (pooled p<0.05) only

estimate.conbf se.conbf ll.conbf ul.conbf z.conbf p.conbf p.adjust.conbf
k__bacteria.p__firmicutes 0.29 0.0810164 0.13 0.45 3.568494 0.0004 0.0022
k__bacteria.p__verrucomicrobia 0.19 0.0798894 0.03 0.35 2.381818 0.0172 0.0517
k__bacteria.p__bacteroidetes 0.22 0.0979174 0.02 0.41 2.201999 0.0277 0.0553

Order (l4)

Significant only

estimate.conbf se.conbf ll.conbf ul.conbf z.conbf p.conbf p.adjust.conbf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales 0.39 0.0632438 0.27 0.52 6.205840 0.0000 0.0000
k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales 0.32 0.0545196 0.21 0.42 5.793673 0.0000 0.0000
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pasteurellales -0.22 0.0645356 -0.34 -0.09 -3.376832 0.0007 0.0045
k__bacteria.p__firmicutes.c__bacilli.o__bacillales -0.17 0.0523488 -0.28 -0.07 -3.307732 0.0009 0.0050
k__bacteria.p__verrucomicrobia.c__verrucomicrobiae.o__verrucomicrobiales 0.19 0.0798894 0.03 0.35 2.381865 0.0172 0.0637
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.23 0.1084234 0.02 0.44 2.121104 0.0339 0.0965
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.20 0.0958110 0.01 0.39 2.062503 0.0392 0.0966

Family (l5)

Significant only

estimate.conbf se.conbf ll.conbf ul.conbf z.conbf p.conbf p.adjust.conbf
k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae 0.32 0.0545196 0.21 0.42 5.793673 0.0000 0.0000
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pasteurellales.f__pasteurellaceae -0.22 0.0645356 -0.34 -0.09 -3.376832 0.0007 0.0070
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae -0.18 0.0598847 -0.30 -0.07 -3.074603 0.0021 0.0160
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__peptostreptococcaceae 0.19 0.0716934 0.05 0.33 2.637485 0.0084 0.0577
k__bacteria.p__verrucomicrobia.c__verrucomicrobiae.o__verrucomicrobiales.f__verrucomicrobiaceae 0.19 0.0798894 0.03 0.35 2.381865 0.0172 0.0873
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__ruminococcaceae 0.20 0.0874835 0.03 0.38 2.337166 0.0194 0.0923
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae 0.14 0.0667077 0.01 0.27 2.127078 0.0334 0.1234
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae 0.34 0.1598501 0.03 0.65 2.118964 0.0341 0.1234
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.20 0.0958110 0.01 0.39 2.062503 0.0392 0.1240

Genus (l6)

Significant only

estimate.conbf se.conbf ll.conbf ul.conbf z.conbf p.conbf p.adjust.conbf
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__coprococcus 0.33 0.0063390 0.32 0.34 52.048471 0.0000 0.0000
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__blautia 0.38 0.0668433 0.25 0.51 5.708296 0.0000 0.0000
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.38 0.0787618 0.23 0.53 4.829656 0.0000 0.0000
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__ 0.34 0.0781848 0.18 0.49 4.309681 0.0000 0.0003
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pasteurellales.f__pasteurellaceae.g__haemophilus -0.23 0.0652393 -0.36 -0.10 -3.495496 0.0005 0.0064
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae.g__staphylococcus -0.18 0.0594315 -0.30 -0.07 -3.078824 0.0021 0.0196
k__bacteria.p__verrucomicrobia.c__verrucomicrobiae.o__verrucomicrobiales.f__verrucomicrobiaceae.g__akkermansia 0.19 0.0798897 0.03 0.35 2.387877 0.0169 0.1167
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__peptostreptococcaceae.g__ 0.29 0.1410017 0.01 0.57 2.064129 0.0390 0.1823

Meta-analysis of KEGG pathway relative abundance

Change in non-exbf vs. exbf

Level 2 KEGG pathway

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.05 0.0172713 -0.08 -0.01 -2.770421 0.0056 0.1417
Genetic.Information.Processing..Transcription 0.02 0.0059866 0.00 0.03 2.666664 0.0077 0.1417
Metabolism..Carbohydrate.Metabolism 0.01 0.0063844 0.00 0.03 2.183138 0.0290 0.3580

Nice plot

Level 3 KEGG pathway

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.08 0.0153155 0.05 0.11 5.095314 0.0000 0.0001
Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.06 0.0148455 -0.09 -0.03 -4.278043 0.0000 0.0021
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.09 0.0243173 -0.14 -0.04 -3.669960 0.0002 0.0180
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.06 0.0187795 0.03 0.10 3.380198 0.0007 0.0380
Metabolism..Lipid.Metabolism..Fatty.acid.biosynthesis 0.04 0.0129610 0.02 0.07 3.335177 0.0009 0.0380
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.03 0.0089990 -0.05 -0.01 -3.276602 0.0011 0.0390
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Biosynthesis.of.ansamycins 0.08 0.0244139 0.03 0.13 3.197788 0.0014 0.0441
Metabolism..Carbohydrate.Metabolism..Pentose.phosphate.pathway 0.04 0.0119244 0.01 0.06 3.070645 0.0021 0.0595
Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.07 0.0242623 -0.12 -0.02 -2.871463 0.0041 0.1012
Organismal.Systems..Endocrine.System..Adipocytokine.signaling.pathway -0.12 0.0415301 -0.20 -0.04 -2.817180 0.0048 0.1080
Genetic.Information.Processing..Replication.and.Repair..Base.excision.repair 0.01 0.0053033 0.00 0.03 2.758214 0.0058 0.1178
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Xylene.degradation -0.04 0.0176901 -0.08 -0.01 -2.498851 0.0125 0.2194
Metabolism..Energy.Metabolism..Carbon.fixation.in.photosynthetic.organisms 0.03 0.0128413 0.01 0.06 2.485508 0.0129 0.2194
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…other.enzymes 0.03 0.0131930 0.01 0.06 2.463122 0.0138 0.2194
Unclassified..Genetic.Information.Processing..Protein.folding.and.associated.processing -0.01 0.0049931 -0.02 0.00 -2.308193 0.0210 0.3120
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Nicotinate.and.nicotinamide.metabolism -0.03 0.0143473 -0.06 0.00 -2.218663 0.0265 0.3293
Unclassified..Cellular.Processes.and.Signaling..Inorganic.ion.transport.and.metabolism -0.07 0.0338473 -0.14 -0.01 -2.211755 0.0270 0.3293
Organismal.Systems..Endocrine.System..Insulin.signaling.pathway 0.06 0.0270235 0.01 0.11 2.188835 0.0286 0.3293
Metabolism..Carbohydrate.Metabolism..Amino.sugar.and.nucleotide.sugar.metabolism 0.03 0.0134249 0.00 0.06 2.148825 0.0316 0.3293
Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.02 0.0099554 0.00 0.04 2.144209 0.0320 0.3293
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…cytochrome.P450 -0.10 0.0469254 -0.19 -0.01 -2.136785 0.0326 0.3293
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Toluene.degradation -0.07 0.0334904 -0.14 -0.01 -2.123440 0.0337 0.3293
Metabolism..Lipid.Metabolism..Glycerolipid.metabolism 0.03 0.0164356 0.00 0.07 2.120529 0.0340 0.3293
Metabolism..Glycan.Biosynthesis.and.Metabolism..Glycosphingolipid.biosynthesis…globo.series 0.08 0.0401464 0.00 0.16 1.996258 0.0459 0.4265

Nice plot all pathways

Nice plot significant pathways only (pooled p<0.05)

Nice plot multiple testing adjusted significant pathways only (adjusted pooled p<0.1)

Sensitivity analysis

No Haiti data

Level 2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Organismal.Systems..Environmental.Adaptation 0.05 0.0154241 0.02 0.08 3.171071 0.0015 0.0562
Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.05 0.0176124 -0.08 -0.02 -2.850687 0.0044 0.0807
Genetic.Information.Processing..Transcription 0.02 0.0063860 0.00 0.03 2.562214 0.0104 0.1283
Metabolism..Carbohydrate.Metabolism 0.01 0.0066286 0.00 0.03 1.976019 0.0482 0.4454

Level 3

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.08 0.0162836 0.05 0.11 4.954756 0.0000 0.0002
Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.07 0.0150202 -0.09 -0.04 -4.332715 0.0000 0.0016
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.09 0.0230967 -0.14 -0.05 -4.106429 0.0000 0.0030
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.07 0.0182025 0.03 0.10 3.626040 0.0003 0.0161
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Biosynthesis.of.ansamycins 0.09 0.0249367 0.04 0.14 3.532866 0.0004 0.0184
Metabolism..Carbohydrate.Metabolism..Pentose.phosphate.pathway 0.04 0.0119845 0.02 0.06 3.311236 0.0009 0.0302
Organismal.Systems..Environmental.Adaptation..Plant.pathogen.interaction 0.05 0.0139004 0.02 0.07 3.307211 0.0009 0.0302
Metabolism..Lipid.Metabolism..Fatty.acid.biosynthesis 0.04 0.0142889 0.02 0.07 3.104340 0.0019 0.0534
Organismal.Systems..Endocrine.System..Adipocytokine.signaling.pathway -0.13 0.0422790 -0.21 -0.05 -3.025693 0.0025 0.0617
Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.07 0.0243975 -0.12 -0.02 -2.921727 0.0035 0.0780
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.03 0.0100993 -0.05 -0.01 -2.887504 0.0039 0.0791
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Porphyrin.and.chlorophyll.metabolism 0.06 0.0223847 0.02 0.11 2.798977 0.0051 0.0957
Metabolism..Energy.Metabolism..Carbon.fixation.in.photosynthetic.organisms 0.04 0.0131564 0.01 0.06 2.766949 0.0057 0.0975
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…other.enzymes 0.04 0.0131936 0.01 0.06 2.676042 0.0074 0.1192
Genetic.Information.Processing..Replication.and.Repair..Base.excision.repair 0.01 0.0057662 0.00 0.03 2.578692 0.0099 0.1481
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Biotin.metabolism 0.04 0.0180359 0.01 0.08 2.458094 0.0140 0.1955
Unclassified..Cellular.Processes.and.Signaling..Inorganic.ion.transport.and.metabolism -0.09 0.0365552 -0.16 -0.01 -2.365195 0.0180 0.2374
Metabolism..Lipid.Metabolism..Glycerolipid.metabolism 0.04 0.0163608 0.01 0.07 2.333573 0.0196 0.2441
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Toluene.degradation -0.08 0.0346447 -0.15 -0.01 -2.278094 0.0227 0.2625
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…cytochrome.P450 -0.11 0.0475573 -0.20 -0.01 -2.266188 0.0234 0.2625
Organismal.Systems..Endocrine.System..Insulin.signaling.pathway 0.06 0.0275299 0.01 0.11 2.195500 0.0281 0.2935
Unclassified..Genetic.Information.Processing..Protein.folding.and.associated.processing -0.01 0.0050446 -0.02 0.00 -2.185914 0.0288 0.2935
Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.02 0.0100331 0.00 0.04 2.131286 0.0331 0.3220
Metabolism..Amino.Acid.Metabolism..Glycine..serine.and.threonine.metabolism -0.02 0.0072327 -0.03 0.00 -2.100542 0.0357 0.3249
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Nicotinate.and.nicotinamide.metabolism -0.03 0.0156436 -0.06 0.00 -2.088358 0.0368 0.3249
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Metabolism.of.xenobiotics.by.cytochrome.P450 -0.10 0.0480715 -0.19 -0.01 -2.067137 0.0387 0.3249
Genetic.Information.Processing..Translation..RNA.transport 0.06 0.0301254 0.00 0.12 2.062518 0.0392 0.3249
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Tetracycline.biosynthesis 0.06 0.0281702 0.00 0.11 1.995717 0.0460 0.3526
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Proteasome -0.10 0.0484326 -0.19 0.00 -1.990020 0.0466 0.3526
Human.Diseases..Infectious.Diseases..Epithelial.cell.signaling.in.Helicobacter.pylori.infection 0.05 0.0231344 0.00 0.09 1.981795 0.0475 0.3526
Metabolism..Carbohydrate.Metabolism..Amino.sugar.and.nucleotide.sugar.metabolism 0.03 0.0143536 0.00 0.06 1.970387 0.0488 0.3526

No USA(CA_MA_MO) data

Level 2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Glycan.Biosynthesis.and.Metabolism 0.05 0.0115747 0.03 0.07 4.488883 0.0000 0.0003
Genetic.Information.Processing..Transcription 0.01 0.0051201 0.00 0.02 2.738122 0.0062 0.1143
Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.05 0.0186842 -0.08 -0.01 -2.483537 0.0130 0.1604

Level 3

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.07 0.0140831 0.04 0.10 4.940987 0.0000 0.0002
Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.06 0.0158836 -0.09 -0.03 -3.738054 0.0002 0.0210
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Xylene.degradation -0.06 0.0186649 -0.09 -0.02 -2.999156 0.0027 0.1536
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.09 0.0298817 -0.15 -0.03 -2.997946 0.0027 0.1536
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Chaperones.and.folding.catalysts 0.02 0.0083216 0.01 0.04 2.908510 0.0036 0.1595
Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.07 0.0246606 -0.12 -0.02 -2.850372 0.0044 0.1595
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.05 0.0179837 0.01 0.09 2.793881 0.0052 0.1595
Metabolism..Lipid.Metabolism..Fatty.acid.biosynthesis 0.05 0.0163147 0.01 0.08 2.767657 0.0056 0.1595
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Biosynthesis.of.ansamycins 0.07 0.0274480 0.02 0.13 2.613593 0.0090 0.2250
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.02 0.0095096 -0.04 -0.01 -2.562315 0.0104 0.2313
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Biotin.metabolism 0.05 0.0190681 0.01 0.09 2.517749 0.0118 0.2313
Metabolism..Carbohydrate.Metabolism..Pentose.phosphate.pathway 0.03 0.0133415 0.01 0.06 2.503966 0.0123 0.2313
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…other.enzymes 0.04 0.0159839 0.01 0.07 2.384403 0.0171 0.2974
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Chloroalkane.and.chloroalkene.degradation -0.04 0.0187390 -0.08 -0.01 -2.350608 0.0187 0.3026
Genetic.Information.Processing..Replication.and.Repair..Base.excision.repair 0.01 0.0059388 0.00 0.03 2.301070 0.0214 0.3222
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…cytochrome.P450 -0.10 0.0486254 -0.20 -0.01 -2.153855 0.0313 0.4117
Environmental.Information.Processing..Signal.Transduction..Phosphatidylinositol.signaling.system 0.02 0.0084431 0.00 0.03 2.151673 0.0314 0.4117
Metabolism..Energy.Metabolism..Carbon.fixation.in.photosynthetic.organisms 0.03 0.0161602 0.00 0.07 2.134681 0.0328 0.4117
Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.02 0.0107085 0.00 0.04 2.090228 0.0366 0.4353
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Proteasome -0.10 0.0500534 -0.20 0.00 -2.026311 0.0427 0.4829

No UNC data

Level 2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.05 0.0174642 -0.08 -0.01 -2.755588 0.0059 0.2168
Genetic.Information.Processing..Transcription 0.02 0.0066440 0.00 0.03 2.404959 0.0162 0.2992

Level 3

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.07 0.0153469 0.04 0.10 4.874259 0.0000 0.0002
Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.06 0.0150010 -0.09 -0.03 -4.232451 0.0000 0.0026
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.09 0.0256901 -0.14 -0.04 -3.356095 0.0008 0.0596
Genetic.Information.Processing..Replication.and.Repair..Base.excision.repair 0.02 0.0054765 0.01 0.03 3.108958 0.0019 0.0875
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.06 0.0201180 0.02 0.10 3.073116 0.0021 0.0875
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Biosynthesis.of.ansamycins 0.08 0.0248949 0.03 0.12 3.045504 0.0023 0.0875
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.03 0.0096273 -0.05 -0.01 -2.972464 0.0030 0.0954
Metabolism..Lipid.Metabolism..Fatty.acid.biosynthesis 0.04 0.0143916 0.01 0.07 2.890399 0.0038 0.1005
Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.07 0.0245939 -0.12 -0.02 -2.878143 0.0040 0.1005
Metabolism..Carbohydrate.Metabolism..Pentose.phosphate.pathway 0.03 0.0122911 0.01 0.06 2.762045 0.0057 0.1298
Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.02 0.0101136 0.00 0.04 2.278763 0.0227 0.4660
Unclassified..Genetic.Information.Processing..Protein.folding.and.associated.processing -0.01 0.0050162 -0.02 0.00 -2.211653 0.0270 0.5078
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…other.enzymes 0.03 0.0142804 0.00 0.06 2.143191 0.0321 0.5078
Organismal.Systems..Endocrine.System..Adipocytokine.signaling.pathway -0.10 0.0493909 -0.20 -0.01 -2.107573 0.0351 0.5078
Metabolism..Energy.Metabolism..Carbon.fixation.in.photosynthetic.organisms 0.03 0.0125598 0.00 0.05 2.100403 0.0357 0.5078
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…cytochrome.P450 -0.10 0.0476250 -0.19 -0.01 -2.097515 0.0359 0.5078
Human.Diseases..Infectious.Diseases..Epithelial.cell.signaling.in.Helicobacter.pylori.infection 0.05 0.0233794 0.00 0.09 2.039309 0.0414 0.5378
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Nicotinate.and.nicotinamide.metabolism -0.03 0.0154611 -0.06 0.00 -2.007333 0.0447 0.5378
Metabolism..Carbohydrate.Metabolism..Amino.sugar.and.nucleotide.sugar.metabolism 0.03 0.0146735 0.00 0.06 1.970575 0.0488 0.5378

stratify by birth mode

Vaginal birth

Level 2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Human.Diseases..Infectious.Diseases -0.05 0.0139289 -0.08 -0.02 -3.481839 0.0005 0.0189
Human.Diseases..Neurodegenerative.Diseases -0.08 0.0286090 -0.14 -0.03 -2.936430 0.0033 0.0631
Unclassified..Genetic.Information.Processing -0.02 0.0083563 -0.04 0.00 -2.428091 0.0152 0.1607
Environmental.Information.Processing..Signal.Transduction -0.06 0.0231749 -0.10 -0.01 -2.388463 0.0169 0.1607
Metabolism..Metabolism.of.Other.Amino.Acids -0.02 0.0076171 -0.03 0.00 -2.197602 0.0280 0.2126

Level 3 All

Significant only (pooled p<0.05)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Carbohydrate.Metabolism..Pentose.phosphate.pathway 0.05 0.0092376 0.03 0.06 5.001030 0.0000 0.0001
Metabolism..Carbohydrate.Metabolism..Propanoate.metabolism -0.06 0.0134718 -0.08 -0.03 -4.234055 0.0000 0.0026
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.10 0.0284718 -0.16 -0.04 -3.488412 0.0005 0.0371
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.07 0.0219622 0.03 0.12 3.280725 0.0010 0.0593
Unclassified..Cellular.Processes.and.Signaling..Sporulation 0.27 0.0880246 0.10 0.44 3.057250 0.0022 0.0994
Metabolism..Carbohydrate.Metabolism..Amino.sugar.and.nucleotide.sugar.metabolism 0.04 0.0132461 0.01 0.07 3.010830 0.0026 0.0994
Metabolism..Enzyme.Families..Peptidases 0.02 0.0072551 0.01 0.04 2.945901 0.0032 0.1053
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Pantothenate.and.CoA.biosynthesis 0.02 0.0086275 0.01 0.04 2.657414 0.0079 0.2155
Metabolism..Energy.Metabolism..Carbon.fixation.in.photosynthetic.organisms 0.03 0.0132238 0.01 0.06 2.600904 0.0093 0.2155
Metabolism..Carbohydrate.Metabolism..Butanoate.metabolism -0.04 0.0152890 -0.07 -0.01 -2.554916 0.0106 0.2155
Metabolism..Metabolism.of.Other.Amino.Acids..Glutathione.metabolism -0.08 0.0298932 -0.13 -0.02 -2.539817 0.0111 0.2155
Metabolism..Amino.Acid.Metabolism..Tryptophan.metabolism -0.10 0.0410760 -0.18 -0.02 -2.524773 0.0116 0.2155
Metabolism..Amino.Acid.Metabolism..Lysine.degradation -0.09 0.0377849 -0.17 -0.02 -2.484310 0.0130 0.2155
Environmental.Information.Processing..Membrane.Transport..Bacterial.secretion.system -0.05 0.0193032 -0.09 -0.01 -2.479047 0.0132 0.2155
Unclassified..Genetic.Information.Processing..Replication..recombination.and.repair.proteins -0.04 0.0181120 -0.08 -0.01 -2.447159 0.0144 0.2198
Environmental.Information.Processing..Signal.Transduction..Two.component.system -0.06 0.0262962 -0.11 -0.01 -2.320034 0.0203 0.2911
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.06 0.0266534 0.01 0.11 2.242983 0.0249 0.3300
Metabolism..Lipid.Metabolism..Sphingolipid.metabolism 0.10 0.0437020 0.01 0.18 2.227115 0.0259 0.3300
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Limonene.and.pinene.degradation -0.08 0.0386717 -0.16 -0.01 -2.104844 0.0353 0.4255
Metabolism..Amino.Acid.Metabolism..Valine..leucine.and.isoleucine.degradation -0.09 0.0434446 -0.17 0.00 -2.060227 0.0394 0.4327
Metabolism..Energy.Metabolism..Methane.metabolism 0.04 0.0173608 0.00 0.07 2.050251 0.0403 0.4327
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.03 0.0162180 -0.06 0.00 -2.025958 0.0428 0.4327
Organismal.Systems..Endocrine.System..Insulin.signaling.pathway 0.07 0.0351516 0.00 0.14 2.001871 0.0453 0.4327
Environmental.Information.Processing..Membrane.Transport..Secretion.system -0.05 0.0255435 -0.10 0.00 -1.992679 0.0463 0.4327
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Biosynthesis.of.ansamycins 0.08 0.0405844 0.00 0.16 1.984209 0.0472 0.4327

Multiple testing adjusted Significant only (adjusted pooled p<0.1)

C-section birth

Level 2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Human.Diseases..Infectious.Diseases -0.11 0.0258973 -0.16 -0.06 -4.350903 0.0000 0.0005
Environmental.Information.Processing..Signal.Transduction -0.14 0.0372818 -0.21 -0.07 -3.799334 0.0001 0.0028
Unclassified..Poorly.Characterized -0.18 0.0692044 -0.32 -0.04 -2.605500 0.0092 0.0868
Metabolism..Energy.Metabolism 0.04 0.0147283 0.01 0.07 2.542920 0.0110 0.0868
Human.Diseases..Neurodegenerative.Diseases -0.14 0.0567741 -0.25 -0.03 -2.529420 0.0114 0.0868
Genetic.Information.Processing..Replication.and.Repair 0.11 0.0472699 0.01 0.20 2.229488 0.0258 0.1311
Metabolism..Nucleotide.Metabolism 0.11 0.0510945 0.01 0.21 2.228820 0.0258 0.1311
Metabolism..Amino.Acid.Metabolism 0.03 0.0117885 0.00 0.05 2.174502 0.0297 0.1311
Unclassified..Cellular.Processes.and.Signaling -0.15 0.0711795 -0.29 -0.01 -2.126222 0.0335 0.1311
Metabolism..Carbohydrate.Metabolism 0.03 0.0121865 0.00 0.05 2.114057 0.0345 0.1311

Level 3 All

Significant only (pooled p<0.05)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Amino.Acid.Metabolism..Lysine.degradation -0.24 0.0589751 -0.36 -0.13 -4.087199 0.0000 0.0052
Environmental.Information.Processing..Membrane.Transport..Secretion.system -0.17 0.0409038 -0.25 -0.09 -4.077994 0.0000 0.0052
Cellular.Processes..Cell.Motility..Cytoskeleton.proteins 0.19 0.0501812 0.10 0.29 3.878754 0.0001 0.0080
Environmental.Information.Processing..Signal.Transduction..Two.component.system -0.16 0.0417345 -0.24 -0.07 -3.745237 0.0002 0.0103
Metabolism..Amino.Acid.Metabolism..Lysine.biosynthesis 0.09 0.0261242 0.04 0.14 3.569470 0.0004 0.0148
Metabolism..Amino.Acid.Metabolism..Tryptophan.metabolism -0.22 0.0612575 -0.34 -0.10 -3.548736 0.0004 0.0148
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Thiamine.metabolism 0.08 0.0227453 0.03 0.12 3.424647 0.0006 0.0201
Metabolism..Lipid.Metabolism..Biosynthesis.of.unsaturated.fatty.acids -0.16 0.0480023 -0.25 -0.07 -3.329941 0.0009 0.0249
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Drug.metabolism…other.enzymes 0.07 0.0212525 0.03 0.11 3.291685 0.0010 0.0253
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.15 0.0458870 -0.24 -0.06 -3.247440 0.0012 0.0267
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Sulfur.relay.system -0.14 0.0433387 -0.22 -0.05 -3.165507 0.0015 0.0300
Metabolism..Carbohydrate.Metabolism..Galactose.metabolism 0.12 0.0364226 0.04 0.19 3.161364 0.0016 0.0300
Genetic.Information.Processing..Replication.and.Repair..Mismatch.repair 0.08 0.0269024 0.03 0.14 3.094126 0.0020 0.0348
Metabolism..Enzyme.Families..Peptidases 0.04 0.0120243 0.01 0.06 3.059696 0.0022 0.0362
Unclassified..Cellular.Processes.and.Signaling..Inorganic.ion.transport.and.metabolism -0.23 0.0753721 -0.38 -0.08 -3.025179 0.0025 0.0379
Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Phenylpropanoid.biosynthesis 0.16 0.0543283 0.06 0.27 2.990393 0.0028 0.0379
Genetic.Information.Processing..Replication.and.Repair..Nucleotide.excision.repair 0.19 0.0633790 0.07 0.31 2.987096 0.0028 0.0379
Metabolism..Carbohydrate.Metabolism..Amino.sugar.and.nucleotide.sugar.metabolism 0.09 0.0289330 0.03 0.14 2.954096 0.0031 0.0379
Genetic.Information.Processing..Replication.and.Repair..DNA.replication.proteins 0.07 0.0241948 0.02 0.12 2.953335 0.0031 0.0379
Unclassified..Cellular.Processes.and.Signaling..Sporulation 0.43 0.1509691 0.13 0.72 2.820915 0.0048 0.0548
Unclassified..Cellular.Processes.and.Signaling..Other.ion.coupled.transporters -0.11 0.0387677 -0.18 -0.03 -2.778113 0.0055 0.0596
Metabolism..Amino.Acid.Metabolism..Valine..leucine.and.isoleucine.degradation -0.15 0.0536771 -0.25 -0.04 -2.713844 0.0067 0.0667
Metabolism..Metabolism.of.Other.Amino.Acids..Glutathione.metabolism -0.12 0.0442873 -0.21 -0.03 -2.709852 0.0067 0.0667
Metabolism..Energy.Metabolism..Carbon.fixation.in.photosynthetic.organisms 0.05 0.0195297 0.01 0.09 2.697465 0.0070 0.0667
Unclassified..Metabolism..Metabolism.of.cofactors.and.vitamins -0.13 0.0498366 -0.23 -0.04 -2.676021 0.0075 0.0682
Human.Diseases..Infectious.Diseases..Vibrio.cholerae.pathogenic.cycle -0.13 0.0476819 -0.22 -0.03 -2.658069 0.0079 0.0692
Metabolism..Nucleotide.Metabolism..Pyrimidine.metabolism 0.11 0.0429456 0.03 0.19 2.571884 0.0101 0.0816
Metabolism..Amino.Acid.Metabolism..Phenylalanine..tyrosine.and.tryptophan.biosynthesis 0.08 0.0298059 0.02 0.13 2.545772 0.0109 0.0816
Unclassified..Poorly.Characterized..Function.unknown -0.16 0.0616904 -0.28 -0.04 -2.543364 0.0110 0.0816
Unclassified..Metabolism..Biosynthesis.and.biodegradation.of.secondary.metabolites -0.22 0.0850259 -0.38 -0.05 -2.538914 0.0111 0.0816
Metabolism..Enzyme.Families..Protein.kinases -0.13 0.0510231 -0.23 -0.03 -2.534648 0.0113 0.0816
Metabolism..Metabolism.of.Cofactors.and.Vitamins..One.carbon.pool.by.folate 0.14 0.0568953 0.03 0.26 2.530320 0.0114 0.0816
Metabolism..Energy.Metabolism..Methane.metabolism 0.06 0.0251859 0.01 0.11 2.516847 0.0118 0.0822
Cellular.Processes..Cell.Growth.and.Death..Cell.cycle…Caulobacter 0.21 0.0840125 0.04 0.37 2.462727 0.0138 0.0929
Genetic.Information.Processing..Replication.and.Repair..DNA.replication 0.10 0.0391391 0.02 0.17 2.444083 0.0145 0.0950
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Ubiquinone.and.other.terpenoid.quinone.biosynthesis -0.13 0.0541391 -0.24 -0.02 -2.391946 0.0168 0.1066
Human.Diseases..Infectious.Diseases..Pertussis -0.35 0.1463292 -0.63 -0.06 -2.363893 0.0181 0.1119
Metabolism..Carbohydrate.Metabolism..Starch.and.sucrose.metabolism 0.10 0.0416485 0.02 0.18 2.325456 0.0200 0.1187
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Polycyclic.aromatic.hydrocarbon.degradation 0.17 0.0745087 0.03 0.32 2.319764 0.0204 0.1187
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Pantothenate.and.CoA.biosynthesis 0.04 0.0172203 0.01 0.07 2.312943 0.0207 0.1187
Unclassified..Cellular.Processes.and.Signaling..Electron.transfer.carriers -0.32 0.1370671 -0.58 -0.05 -2.299820 0.0215 0.1199
Cellular.Processes..Cell.Motility..Bacterial.motility.proteins -0.20 0.0868495 -0.37 -0.03 -2.261725 0.0237 0.1293
Metabolism..Amino.Acid.Metabolism..Amino.acid.related.enzymes 0.10 0.0459318 0.01 0.19 2.240355 0.0251 0.1335
Metabolism..Glycan.Biosynthesis.and.Metabolism..Peptidoglycan.biosynthesis 0.17 0.0742134 0.02 0.31 2.230095 0.0257 0.1337
Metabolism..Glycan.Biosynthesis.and.Metabolism..Lipopolysaccharide.biosynthesis.proteins -0.49 0.2211418 -0.92 -0.06 -2.222040 0.0263 0.1337
Unclassified..Cellular.Processes.and.Signaling..Membrane.and.intracellular.structural.molecules -0.32 0.1470898 -0.61 -0.04 -2.209314 0.0272 0.1338
Metabolism..Energy.Metabolism..Photosynthesis 0.31 0.1402569 0.03 0.58 2.204900 0.0275 0.1338
Metabolism..Energy.Metabolism..Photosynthesis.proteins 0.29 0.1367362 0.02 0.56 2.138483 0.0325 0.1420
Genetic.Information.Processing..Replication.and.Repair..Homologous.recombination 0.15 0.0711988 0.01 0.29 2.136688 0.0326 0.1420
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Protein.export 0.20 0.0937140 0.02 0.38 2.136099 0.0327 0.1420
Metabolism..Lipid.Metabolism..Sphingolipid.metabolism 0.32 0.1483752 0.03 0.61 2.130141 0.0332 0.1420
Genetic.Information.Processing..Translation..Translation.factors 0.20 0.0932695 0.02 0.38 2.122070 0.0338 0.1420
Genetic.Information.Processing..Replication.and.Repair..DNA.repair.and.recombination.proteins 0.14 0.0668713 0.01 0.27 2.117768 0.0342 0.1420
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Prenyltransferases 0.07 0.0325922 0.01 0.13 2.114184 0.0345 0.1420
Unclassified..Poorly.Characterized..General.function.prediction.only -0.15 0.0699906 -0.29 -0.01 -2.113968 0.0345 0.1420
Unclassified..Cellular.Processes.and.Signaling..Signal.transduction.mechanisms -0.12 0.0558385 -0.23 -0.01 -2.111638 0.0347 0.1420
Metabolism..Metabolism.of.Other.Amino.Acids..beta.Alanine.metabolism -0.15 0.0714335 -0.29 -0.01 -2.044687 0.0409 0.1643
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Limonene.and.pinene.degradation -0.18 0.0900308 -0.36 -0.01 -2.035126 0.0418 0.1652
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Biosynthesis.of.siderophore.group.nonribosomal.peptides -0.28 0.1381849 -0.55 -0.01 -2.017012 0.0437 0.1690
Genetic.Information.Processing..Translation..Ribosome 0.26 0.1303595 0.01 0.52 2.011413 0.0443 0.1690
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Toluene.degradation -0.09 0.0471773 -0.19 0.00 -1.997887 0.0457 0.1717
Genetic.Information.Processing..Replication.and.Repair..Chromosome 0.03 0.0141358 0.00 0.06 1.988861 0.0467 0.1725
Metabolism..Carbohydrate.Metabolism..Glyoxylate.and.dicarboxylate.metabolism -0.10 0.0482937 -0.19 0.00 -1.971762 0.0486 0.1768

Multiple testing adjusted Significant only (adjusted pooled p<0.1)

Taxa relative abundance Bangladesh data only

All analyses are adjusted for age of infants or breastfeeding status at sample collection and accounting for repeated/longitudinal sample collection.

Mean taxa relative abundance by duration of exbf in samples > 6 months

For Subramanian (Bangladesh) data only.

Duration of exbf

Change in taxa relative abundance in duration of exclusive bf >2months vs. <=2 months

Phylum (L2)

GAMLSS

estimate se teststat pval pval.adjust ll ul
firmicutes -0.25 0.0633103 -3.872828 0.0001 0.0005 -0.37 -0.12
actinobacteria 0.23 0.0709545 3.196223 0.0015 0.0029 0.09 0.37

Order (l4)

GAMLSS

estimate se teststat pval pval.adjust ll ul
actinobacteria.c__coriobacteriia.o__coriobacteriales -0.25 0.0652555 -3.808244 0.0002 0.0007 -0.38 -0.12
firmicutes.c__bacilli.o__lactobacillales -0.27 0.0725448 -3.729979 0.0002 0.0007 -0.41 -0.13
actinobacteria.c__actinobacteria.o__bifidobacteriales 0.25 0.0712188 3.570704 0.0004 0.0009 0.11 0.39
firmicutes.c__erysipelotrichi.o__erysipelotrichales -0.15 0.0757899 -2.010438 0.0448 0.0784 -0.30 0.00

Family (L5)

Grey

GAMLSS

estimate se teststat pval pval.adjust ll ul
firmicutes.c__bacilli.o__lactobacillales.f__lactobacillaceae -0.31 0.0757692 -4.099792 0.0000 0.0006 -0.46 -0.16
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae -0.25 0.0652555 -3.808244 0.0002 0.0010 -0.38 -0.12
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae 0.25 0.0712188 3.570704 0.0004 0.0017 0.11 0.39
bacteroidetes.c__bacteroidia.o__bacteroidales.f__prevotellaceae -0.27 0.0800336 -3.353959 0.0008 0.0027 -0.43 -0.11
firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae -0.22 0.0799003 -2.719980 0.0067 0.0174 -0.37 -0.06
firmicutes.c__bacilli.o__lactobacillales.f__enterococcaceae 0.19 0.0817407 2.344727 0.0193 0.0419 0.03 0.35
firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae -0.15 0.0757899 -2.010438 0.0448 0.0789 -0.30 0.00
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae -0.14 0.0722439 -1.976243 0.0486 0.0789 -0.28 0.00

Genus (L6)

GAMLSS

estimate se teststat pval pval.adjust ll ul
firmicutes.c__bacilli.o__lactobacillales.f__lactobacillaceae.g__lactobacillus -0.33 0.0755929 -4.385561 0.0000 0.0003 -0.48 -0.18
firmicutes.c__clostridia.oclostridiales.f.g__ -0.34 0.0803138 -4.190128 0.0000 0.0003 -0.49 -0.18
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium 0.25 0.0712187 3.570578 0.0004 0.0027 0.11 0.39
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__.ruminococcus. -0.25 0.0741715 -3.393195 0.0007 0.0035 -0.40 -0.11
bacteroidetes.c__bacteroidia.o__bacteroidales.f__prevotellaceae.g__prevotella -0.27 0.0800336 -3.353932 0.0008 0.0035 -0.43 -0.11
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__ -0.22 0.0720564 -3.016054 0.0027 0.0093 -0.36 -0.08
firmicutes.c__clostridia.o__clostridiales.f__clostridiaceae.g__ -0.24 0.0847773 -2.866116 0.0043 0.0129 -0.41 -0.08
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__blautia -0.22 0.0791422 -2.768889 0.0058 0.0152 -0.37 -0.06
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__collinsella -0.17 0.0682455 -2.504614 0.0125 0.0292 -0.30 -0.04
firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__catenibacterium -0.23 0.0955240 -2.404645 0.0165 0.0346 -0.42 -0.04
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__ -0.16 0.0722253 -2.233574 0.0259 0.0494 -0.30 -0.02
firmicutes.c__bacilli.o__lactobacillales.f__enterococcaceae.g__enterococcus 0.18 0.0833351 2.161482 0.0310 0.0543 0.02 0.34

Modification effect of breastfeeding status on samples of patients with vs. without diarrhea at sample collection

Subramania (Bangladesh) data only.

Taxa relative abundance in samples of patients with vs. without diarrhea at sample collection

Only LME was used as GAMLSS has issues with small sample size (when stratifying). LME as showed above has lower power than GAMLSS in general.

After 6 month

Stratified by duration of exclusive bf

Family

GAMLSS

In infants with duration of exclusive bf <=2 months

estimate se teststat pval pval.adjust ll ul
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae -0.77 0.1993835 -3.869376 0.0001 0.0017 -1.16 -0.38
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae -0.69 0.1960537 -3.525664 0.0005 0.0031 -1.08 -0.31
firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae 0.53 0.1836007 2.865417 0.0044 0.0191 0.17 0.89

In infants with duration of exclusive bf >2 months

estimate se teststat pval pval.adjust ll ul ——— — ——— —– ———— — —

Genus

GAMLSS

In infants with duration of exclusive bf <=2 months

estimate se teststat pval pval.adjust ll ul
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium -0.77 0.1993838 -3.869325 0.0001 0.0027 -1.16 -0.38
firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae.g__streptococcus 0.52 0.1841506 2.847491 0.0046 0.0488 0.16 0.89
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__collinsella -0.50 0.2105904 -2.370786 0.0183 0.1237 -0.91 -0.09
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__ -0.50 0.2188542 -2.273476 0.0236 0.1237 -0.93 -0.07

In infants with duration of exclusive bf >2 months

estimate se teststat pval pval.adjust ll ul
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__ 0.39 0.2285308 1.688668 0.0923 0.9809 -0.06 0.83

Stratified by bf status

Family

GAMLSS

In non-exclusive bf infants

estimate se teststat pval pval.adjust ll ul
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae -0.34 0.1461708 -2.353678 0.0189 0.2458 -0.63 -0.06
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae -0.25 0.1516653 -1.656799 0.0981 0.4727 -0.55 0.05

In no bf infants

estimate se teststat pval pval.adjust ll ul
firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae 2.09 0.6246379 3.347308 0.0018 0.0228 0.87 3.32
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae -1.84 0.7653211 -2.404776 0.0208 0.1351 -3.34 -0.34
Genus

GAMLSS

In bf infants

estimate se teststat pval pval.adjust ll ul
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__collinsella -0.29 0.1480753 -1.965286 0.0498 0.6547 -0.58 0.00
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium -0.25 0.1516657 -1.656853 0.0981 0.6547 -0.55 0.05

In non-bf infants

estimate se teststat pval pval.adjust ll ul
firmicutes.c__bacilli.o__lactobacillales.f__streptococcaceae.g__streptococcus 2.09 0.6249206 3.337650 0.0018 0.0379 0.86 3.31
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium -1.84 0.7653209 -2.404758 0.0208 0.2182 -3.34 -0.34

microbiota age in samples of infants with vs. without diarrhea at sample collection stratified by duration of exclusive breastfeeding

With GAMM fit and 95%CI.

LME fit <=2 months

GAM part

Estimate Std. Error t value Pr(>|t|)
(Intercept) 10.3788398 0.2835665 36.6010753 0.0000000
dia.exbf2No.>2 months -1.1507899 0.4879123 -2.3585999 0.0186104
dia.exbf2Yes.<=2 months -1.1945958 0.4839537 -2.4684094 0.0138028
dia.exbf2Yes.>2 months -0.5097696 0.8117265 -0.6280066 0.5301988
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 5.032806 5.032806 251.05395 0
s(age.sample):dia.exbf2No.>2 months 4.191756 4.191756 149.07931 0
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 37.58735 0
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 49.79342 0

LME part

Value Std.Error DF t-value p-value
X(Intercept) 10.3788398 0.2843456 689 36.500798 0.0000000
Xdia.exbf2No.>2 months -1.1507899 0.4892527 689 -2.352138 0.0189463
Xdia.exbf2Yes.<=2 months -1.1945958 0.4852832 689 -2.461647 0.0140740
Xdia.exbf2Yes.>2 months -0.5097696 0.8139565 689 -0.626286 0.5313348
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 1.8308388 1.3486999 689 1.357484 0.1750718
Xs(age.sample):dia.exbf2No.>2 monthsFx1 1.6657329 1.3242074 689 1.257909 0.2088507
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 3.4720580 0.5678815 689 6.114054 0.0000000
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 5.0913209 0.7234958 689 7.037112 0.0000000

Test for heterogeneity (interaction)

Estimate Std. Error t value p.val
(Intercept) 3.7678265 0.3316981 11.359203 0.0000000
age.sample 0.6832422 0.0173814 39.308910 0.0000000
month.exbf2>2 months -1.2353814 0.5064509 -2.439291 0.0147161
diarrheaYes -1.0072569 0.5024243 -2.004793 0.0449851
month.exbf2>2 months:diarrheaYes 1.8143024 0.9006571 2.014421 0.0439654

Alpha diversity in samples of infants with vs. without diarrhea at sample collection stratified by duration of exclusive breastfeeding

With GAMM fit and 95%CI.

Shannon

Estimate Std. Error t value Pr(>|t|)
(Intercept) 3.0665206 0.0823202 37.2511259 0.0000000
dia.exbf2No.>2 months -0.1567257 0.1292484 -1.2125925 0.2255782
dia.exbf2Yes.<=2 months -0.5837970 0.1257959 -4.6408273 0.0000039
dia.exbf2Yes.>2 months -0.0919724 0.1901039 -0.4838004 0.6286357
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 1.000000 1.000000 511.09021 0.00e+00
s(age.sample):dia.exbf2No.>2 months 5.974811 5.974811 75.05942 0.00e+00
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 15.96302 6.93e-05
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 43.95975 0.00e+00
Value Std.Error DF t-value p-value
X(Intercept) 3.0665206 0.0824874 935 37.175641 0.0000000
Xdia.exbf2No.>2 months -0.1567257 0.1295109 935 -1.210135 0.2265328
Xdia.exbf2Yes.<=2 months -0.5837970 0.1260513 935 -4.631425 0.0000041
Xdia.exbf2Yes.>2 months -0.0919724 0.1904900 935 -0.482820 0.6293366
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 0.8428954 0.0373599 935 22.561490 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 -0.7155803 0.5005884 935 -1.429479 0.1532008
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 0.5554706 0.1393107 935 3.987278 0.0000720
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 0.9760833 0.1475164 935 6.616780 0.0000000

GAM part

Estimate Std. Error t value Pr(>|t|)
(Intercept) 3.0665206 0.0823202 37.2511259 0.0000000
dia.exbf2No.>2 months -0.1567257 0.1292484 -1.2125925 0.2255782
dia.exbf2Yes.<=2 months -0.5837970 0.1257959 -4.6408273 0.0000039
dia.exbf2Yes.>2 months -0.0919724 0.1901039 -0.4838004 0.6286357
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 1.000000 1.000000 511.09021 0.00e+00
s(age.sample):dia.exbf2No.>2 months 5.974811 5.974811 75.05942 0.00e+00
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 15.96302 6.93e-05
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 43.95975 0.00e+00

LME part

Value Std.Error DF t-value p-value
X(Intercept) 3.0665206 0.0824874 935 37.175641 0.0000000
Xdia.exbf2No.>2 months -0.1567257 0.1295109 935 -1.210135 0.2265328
Xdia.exbf2Yes.<=2 months -0.5837970 0.1260513 935 -4.631425 0.0000041
Xdia.exbf2Yes.>2 months -0.0919724 0.1904900 935 -0.482820 0.6293366
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 0.8428954 0.0373599 935 22.561490 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 -0.7155803 0.5005884 935 -1.429479 0.1532008
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 0.5554706 0.1393107 935 3.987278 0.0000720
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 0.9760833 0.1475164 935 6.616780 0.0000000

Test for heterogeneity (interaction)

Estimate Std. Error t value p.val
(Intercept) 1.8029966 0.0917394 19.653450 0.0000000
age.sample 0.1228124 0.0040692 30.181133 0.0000000
month.exbf2>2 months -0.1604039 0.1316082 -1.218798 0.2229207
diarrheaYes -0.5210706 0.1247534 -4.176806 0.0000296
month.exbf2>2 months:diarrheaYes 0.5706337 0.1973949 2.890823 0.0038423

Observed_species

Estimate Std. Error t value Pr(>|t|)
(Intercept) 151.196675 8.778134 17.2242389 0.0000000
dia.exbf2No.>2 months 6.376610 13.831570 0.4610185 0.6448877
dia.exbf2Yes.<=2 months -32.741233 8.978024 -3.6468195 0.0002795
dia.exbf2Yes.>2 months 8.288239 17.024836 0.4868322 0.6264862
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 2.241236 2.241236 186.022933 0.0000000
s(age.sample):dia.exbf2No.>2 months 4.803475 4.803475 86.288380 0.0000000
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 9.841034 0.0017564
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 34.546738 0.0000000
Value Std.Error DF t-value p-value
X(Intercept) 151.196675 8.795958 935 17.1893366 0.0000000
Xdia.exbf2No.>2 months 6.376610 13.859654 935 0.4600843 0.6455627
Xdia.exbf2Yes.<=2 months -32.741233 8.996254 935 -3.6394298 0.0002882
Xdia.exbf2Yes.>2 months 8.288239 17.059405 935 0.4858457 0.6271904
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 51.801469 8.730802 935 5.9331857 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 -19.877541 26.849174 935 -0.7403409 0.4592790
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 31.121465 9.940785 935 3.1306850 0.0017981
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 61.612841 10.503858 935 5.8657345 0.0000000

GAM part

Estimate Std. Error t value Pr(>|t|)
(Intercept) 151.196675 8.778134 17.2242389 0.0000000
dia.exbf2No.>2 months 6.376610 13.831570 0.4610185 0.6448877
dia.exbf2Yes.<=2 months -32.741233 8.978024 -3.6468195 0.0002795
dia.exbf2Yes.>2 months 8.288239 17.024836 0.4868322 0.6264862
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 2.241236 2.241236 186.022933 0.0000000
s(age.sample):dia.exbf2No.>2 months 4.803475 4.803475 86.288380 0.0000000
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 9.841034 0.0017564
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 34.546738 0.0000000

LME part

Value Std.Error DF t-value p-value
X(Intercept) 151.196675 8.795958 935 17.1893366 0.0000000
Xdia.exbf2No.>2 months 6.376610 13.859654 935 0.4600843 0.6455627
Xdia.exbf2Yes.<=2 months -32.741233 8.996254 935 -3.6394298 0.0002882
Xdia.exbf2Yes.>2 months 8.288239 17.059405 935 0.4858457 0.6271904
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 51.801469 8.730802 935 5.9331857 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 -19.877541 26.849174 935 -0.7403409 0.4592790
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 31.121465 9.940785 935 3.1306850 0.0017981
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 61.612841 10.503858 935 5.8657345 0.0000000

Test for heterogeneity (interaction)

Estimate Std. Error t value p.val
(Intercept) 67.218370 9.3632479 7.1789587 0.0000000
age.sample 8.165080 0.2895546 28.1987576 0.0000000
month.exbf2>2 months 6.548791 14.1631117 0.4623836 0.6438062
diarrheaYes -27.156839 8.8730060 -3.0606132 0.0022088
month.exbf2>2 months:diarrheaYes 28.115237 14.0092249 2.0069088 0.0447594

Pd_whole_tree

Estimate Std. Error t value Pr(>|t|)
(Intercept) 11.1473183 0.4242502 26.2753392 0.0000000
dia.exbf2No.>2 months 0.2157323 0.6676390 0.3231271 0.7466679
dia.exbf2Yes.<=2 months -2.4295713 0.5177632 -4.6924371 0.0000031
dia.exbf2Yes.>2 months -0.1330212 0.8797770 -0.1511987 0.8798500
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 1.00000 1.00000 651.06494 0.0e+00
s(age.sample):dia.exbf2No.>2 months 4.26171 4.26171 146.66378 0.0e+00
s(age.sample):dia.exbf2Yes.<=2 months 1.00000 1.00000 20.80080 5.7e-06
s(age.sample):dia.exbf2Yes.>2 months 1.00000 1.00000 48.09244 0.0e+00
Value Std.Error DF t-value p-value
X(Intercept) 11.1473183 0.4251117 935 26.2220945 0.0000000
Xdia.exbf2No.>2 months 0.2157323 0.6689947 935 0.3224723 0.7471670
Xdia.exbf2Yes.<=2 months -2.4295713 0.5188143 935 -4.6829302 0.0000032
Xdia.exbf2Yes.>2 months -0.1330212 0.8815636 935 -0.1508923 0.8800932
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 3.9257946 0.1541688 935 25.4642659 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 0.5241955 1.3248785 935 0.3956555 0.6924494
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 2.6094784 0.5733168 935 4.5515473 0.0000060
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 4.1958246 0.6062613 935 6.9208183 0.0000000

GAM part

Estimate Std. Error t value Pr(>|t|)
(Intercept) 11.1473183 0.4242502 26.2753392 0.0000000
dia.exbf2No.>2 months 0.2157323 0.6676390 0.3231271 0.7466679
dia.exbf2Yes.<=2 months -2.4295713 0.5177632 -4.6924371 0.0000031
dia.exbf2Yes.>2 months -0.1330212 0.8797770 -0.1511987 0.8798500
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 1.00000 1.00000 651.06494 0.0e+00
s(age.sample):dia.exbf2No.>2 months 4.26171 4.26171 146.66378 0.0e+00
s(age.sample):dia.exbf2Yes.<=2 months 1.00000 1.00000 20.80080 5.7e-06
s(age.sample):dia.exbf2Yes.>2 months 1.00000 1.00000 48.09244 0.0e+00

LME part

Value Std.Error DF t-value p-value
X(Intercept) 11.1473183 0.4251117 935 26.2220945 0.0000000
Xdia.exbf2No.>2 months 0.2157323 0.6689947 935 0.3224723 0.7471670
Xdia.exbf2Yes.<=2 months -2.4295713 0.5188143 935 -4.6829302 0.0000032
Xdia.exbf2Yes.>2 months -0.1330212 0.8815636 935 -0.1508923 0.8800932
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 3.9257946 0.1541688 935 25.4642659 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 0.5241955 1.3248785 935 0.3956555 0.6924494
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 2.6094784 0.5733168 935 4.5515473 0.0000060
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 4.1958246 0.6062613 935 6.9208183 0.0000000

Test for heterogeneity (interaction)

Estimate Std. Error t value p.val
(Intercept) 5.1010594 0.4591138 11.1106653 0.0000000
age.sample 0.5894225 0.0166254 35.4531752 0.0000000
month.exbf2>2 months 0.2033228 0.6822247 0.2980291 0.7656809
diarrheaYes -2.1261538 0.5095509 -4.1726032 0.0000301
month.exbf2>2 months:diarrheaYes 1.7538795 0.8050786 2.1785195 0.0293674

Chao1

Estimate Std. Error t value Pr(>|t|)
(Intercept) 367.19115 24.93875 14.7237215 0.0000000
dia.exbf2No.>2 months 16.36035 39.31689 0.4161151 0.6774169
dia.exbf2Yes.<=2 months -86.62794 23.43335 -3.6967801 0.0002305
dia.exbf2Yes.>2 months 28.78746 47.08230 0.6114285 0.5410577
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 1.502023 1.502023 261.413376 0.0000000
s(age.sample):dia.exbf2No.>2 months 4.677640 4.677640 76.504447 0.0000000
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 7.810505 0.0052936
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 29.909461 0.0000001
Value Std.Error DF t-value p-value
X(Intercept) 367.19115 24.98938 935 14.6938872 0.0000000
Xdia.exbf2No.>2 months 16.36035 39.39672 935 0.4152720 0.6780381
Xdia.exbf2Yes.<=2 months -86.62794 23.48093 935 -3.6892894 0.0002379
Xdia.exbf2Yes.>2 months 28.78746 47.17789 935 0.6101897 0.5418844
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 134.05173 12.55943 935 10.6733923 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 -43.96611 67.65832 935 -0.6498257 0.5159644
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 72.36395 25.94559 935 2.7890649 0.0053934
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 149.59600 27.40922 935 5.4578722 0.0000001

GAM part

Estimate Std. Error t value Pr(>|t|)
(Intercept) 367.19115 24.93875 14.7237215 0.0000000
dia.exbf2No.>2 months 16.36035 39.31689 0.4161151 0.6774169
dia.exbf2Yes.<=2 months -86.62794 23.43335 -3.6967801 0.0002305
dia.exbf2Yes.>2 months 28.78746 47.08230 0.6114285 0.5410577
edf Ref.df F p-value
s(age.sample):dia.exbf2No.<=2 months 1.502023 1.502023 261.413376 0.0000000
s(age.sample):dia.exbf2No.>2 months 4.677640 4.677640 76.504447 0.0000000
s(age.sample):dia.exbf2Yes.<=2 months 1.000000 1.000000 7.810505 0.0052936
s(age.sample):dia.exbf2Yes.>2 months 1.000000 1.000000 29.909461 0.0000001

LME part

Value Std.Error DF t-value p-value
X(Intercept) 367.19115 24.98938 935 14.6938872 0.0000000
Xdia.exbf2No.>2 months 16.36035 39.39672 935 0.4152720 0.6780381
Xdia.exbf2Yes.<=2 months -86.62794 23.48093 935 -3.6892894 0.0002379
Xdia.exbf2Yes.>2 months 28.78746 47.17789 935 0.6101897 0.5418844
Xs(age.sample):dia.exbf2No.<=2 monthsFx1 134.05173 12.55943 935 10.6733923 0.0000000
Xs(age.sample):dia.exbf2No.>2 monthsFx1 -43.96611 67.65832 935 -0.6498257 0.5159644
Xs(age.sample):dia.exbf2Yes.<=2 monthsFx1 72.36395 25.94559 935 2.7890649 0.0053934
Xs(age.sample):dia.exbf2Yes.>2 monthsFx1 149.59600 27.40922 935 5.4578722 0.0000001

Test for heterogeneity (interaction)

Estimate Std. Error t value p.val
(Intercept) 161.48642 26.4705453 6.1006078 0.0000000
age.sample 20.00874 0.7538543 26.5419213 0.0000000
month.exbf2>2 months 16.28471 40.3235504 0.4038512 0.6863222
diarrheaYes -72.27871 23.0991493 -3.1290636 0.0017536
month.exbf2>2 months:diarrheaYes 83.14805 36.4602574 2.2805118 0.0225774

Meta-analysis non-EBF vs. EBF adjusting for age and gender

For comparison: adjusting for age only

Bangladesh data: Non-EBF vs. EBF adjusting for age

Alpha diversity

estimate.nebf ll ul pval.nebf index
0.07 -0.01 0.15 0.1028 chao1
0.07 -0.01 0.15 0.0990 observed_species
0.10 0.02 0.17 0.0136 pd_whole_tree
0.26 0.12 0.40 0.0003 shannon

Microbiota age

Estimate Std. Error df t value Pr(>|t|) ll ul pop
bfNon_exclusiveBF 0.06 0.0598450 212.4315 0.9491631 0.3436 -0.06 0.17 Bangladesh
bfNo_BF -0.08 0.1742787 249.9866 -0.4524857 0.6513 -0.42 0.26 Bangladesh
age.sample 0.09 0.0142278 236.2014 6.1990475 0.0000 0.06 0.12 Bangladesh

Taxa relative abundance

Phylum

estimate se teststat pval pval.adjust ll ul
proteobacteria 0.37 0.1333990 2.808734 0.0053 0.0249 0.11 0.64
actinobacteria -0.37 0.1398279 -2.658182 0.0083 0.0249 -0.65 -0.10
firmicutes 0.24 0.1195704 1.996826 0.0468 0.0749 0.00 0.47
bacteroidetes 0.26 0.1345960 1.968538 0.0499 0.0749 0.00 0.53

Order

estimate se teststat pval pval.adjust ll ul
proteobacteria.c__epsilonproteobacteria.o__campylobacterales 0.92 0.2290519 4.021387 0.0001 0.0014 0.47 1.37
proteobacteria.c__gammaproteobacteria.o__enterobacteriales 0.38 0.1334088 2.833506 0.0049 0.0287 0.12 0.64
actinobacteria.c__actinobacteria.o__bifidobacteriales -0.39 0.1410203 -2.800917 0.0054 0.0287 -0.67 -0.12
actinobacteria.c__coriobacteriia.o__coriobacteriales 0.28 0.1324409 2.119518 0.0349 0.1258 0.02 0.54
firmicutes.c__bacilli.o__lactobacillales 0.25 0.1209641 2.090957 0.0374 0.1258 0.02 0.49

Family

estimate se teststat pval pval.adjust ll ul
firmicutes.c__clostridia.o__clostridiales.f__eubacteriaceae -2.00 0.3808437 -5.248336 0.0000 0.0000 -2.75 -1.25
proteobacteria.c__epsilonproteobacteria.o__campylobacterales.f__campylobacteraceae 0.96 0.2339144 4.104901 0.0001 0.0015 0.50 1.42
proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae 0.38 0.1334088 2.833506 0.0049 0.0400 0.12 0.64
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae -0.39 0.1410203 -2.800917 0.0054 0.0400 -0.67 -0.12
proteobacteria.c__gammaproteobacteria.o__aeromonadales.f__aeromonadaceae 1.16 0.4709172 2.459184 0.0145 0.0887 0.24 2.08
proteobacteria.c__betaproteobacteria.o__burkholderiales.f__alcaligenaceae -1.07 0.4406262 -2.438548 0.0153 0.0887 -1.94 -0.21
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae 0.28 0.1324409 2.119518 0.0349 0.1664 0.02 0.54
bacteroidetes.c__bacteroidia.o__bacteroidales.f__porphyromonadaceae 0.73 0.3545195 2.060785 0.0402 0.1714 0.04 1.43
firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae -0.27 0.1351554 -1.986715 0.0479 0.1839 -0.53 0.00

Genus

estimate se teststat pval pval.adjust ll ul
firmicutes.c__clostridia.o__clostridiales.f__eubacteriaceae.g__pseudoramibacter_eubacterium -2.00 0.3808437 -5.248336 0.0000 0.0000 -2.75 -1.25
proteobacteria.c__epsilonproteobacteria.o__campylobacterales.f__campylobacteraceae.g__campylobacter 0.96 0.2339144 4.104901 0.0001 0.0021 0.50 1.42
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__.ruminococcus. 0.57 0.1969947 2.918040 0.0038 0.0534 0.19 0.96
firmicutes.c__bacilli.o__bacillales.f__bacillaceae.g__ 1.28 0.4543072 2.816733 0.0052 0.0534 0.39 2.17
proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae.g__ 0.38 0.1332888 2.814373 0.0052 0.0534 0.11 0.64
actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium -0.39 0.1410191 -2.800806 0.0054 0.0534 -0.67 -0.12
actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__ 0.42 0.1610534 2.619946 0.0093 0.0815 0.11 0.74
proteobacteria.c__gammaproteobacteria.o__aeromonadales.f__aeromonadaceae.g__ 1.15 0.4709164 2.447941 0.0149 0.1164 0.23 2.08
firmicutes.c__clostridia.o__clostridiales.f__peptostreptococcaceae.g__ 0.68 0.3162457 2.144503 0.0328 0.2244 0.06 1.30
actinobacteria.c__actinobacteria.o__actinomycetales.f__actinomycetaceae.g__actinomyces -0.39 0.1936470 -1.988898 0.0477 0.2528 -0.76 -0.01
firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__clostridium 0.50 0.2523901 1.976217 0.0491 0.2528 0.00 0.99

KEGG pathway

Level 2

estimate se teststat pval pval.adjust ll ul
Metabolism..Glycan.Biosynthesis.and.Metabolism 0.07 0.0163212 4.215017 0.0000 0.0012 0.04 0.10
Metabolism..Amino.Acid.Metabolism -0.04 0.0096992 -3.812500 0.0002 0.0031 -0.06 -0.02
Unclassified..Poorly.Characterized 0.03 0.0095207 3.424841 0.0007 0.0069 0.01 0.05
Unclassified..Metabolism 0.07 0.0203910 3.406482 0.0007 0.0069 0.03 0.11
Metabolism..Lipid.Metabolism 0.02 0.0058624 3.231118 0.0014 0.0093 0.01 0.03
Organismal.Systems..Endocrine.System -0.12 0.0361642 -3.202241 0.0015 0.0093 -0.19 -0.04
Environmental.Information.Processing..Signal.Transduction 0.12 0.0406899 3.006687 0.0029 0.0151 0.04 0.20
Organismal.Systems..Nervous.System -0.06 0.0221222 -2.923405 0.0037 0.0158 -0.11 -0.02
Human.Diseases..Infectious.Diseases 0.05 0.0158343 2.899207 0.0040 0.0158 0.01 0.08
Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.09 0.0309657 -2.847834 0.0047 0.0158 -0.15 -0.03
Cellular.Processes..Transport.and.Catabolism -0.08 0.0270700 -2.829787 0.0050 0.0158 -0.13 -0.02
Unclassified..Cellular.Processes.and.Signaling 0.08 0.0269399 2.818421 0.0051 0.0158 0.02 0.13
Genetic.Information.Processing..Transcription 0.02 0.0068165 2.782895 0.0057 0.0163 0.01 0.03
Metabolism..Metabolism.of.Terpenoids.and.Polyketides 0.01 0.0052916 2.572711 0.0106 0.0272 0.00 0.02
Metabolism..Biosynthesis.of.Other.Secondary.Metabolites -0.04 0.0156097 -2.558534 0.0110 0.0272 -0.07 -0.01
Cellular.Processes..Cell.Motility 0.15 0.0607359 2.500108 0.0129 0.0290 0.03 0.27
Metabolism..Metabolism.of.Other.Amino.Acids 0.01 0.0034517 2.489305 0.0133 0.0290 0.00 0.02
Human.Diseases..Neurodegenerative.Diseases 0.09 0.0382550 2.435313 0.0155 0.0313 0.02 0.17
Metabolism..Xenobiotics.Biodegradation.and.Metabolism 0.03 0.0135599 2.420465 0.0161 0.0313 0.01 0.06
Genetic.Information.Processing..Replication.and.Repair -0.03 0.0119634 -2.135868 0.0335 0.0619 -0.05 0.00
Metabolism..Enzyme.Families -0.01 0.0041515 -2.080651 0.0383 0.0675 -0.02 0.00
Cellular.Processes..Cell.Growth.and.Death -0.03 0.0169356 -2.014184 0.0449 0.0754 -0.07 0.00
Genetic.Information.Processing..Translation -0.03 0.0164401 -1.976600 0.0490 0.0788 -0.06 0.00

Level 3

estimate se teststat pval pval.adjust ll ul
Metabolism..Carbohydrate.Metabolism..C5.Branched.dibasic.acid.metabolism -0.09 0.0214328 -4.337990 0.0000 0.0032 -0.13 -0.05
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Chaperones.and.folding.catalysts 0.04 0.0097145 4.122573 0.0000 0.0032 0.02 0.06
Metabolism..Amino.Acid.Metabolism..Phenylalanine..tyrosine.and.tryptophan.biosynthesis -0.08 0.0202757 -4.075428 0.0001 0.0032 -0.12 -0.04
Metabolism..Amino.Acid.Metabolism..Arginine.and.proline.metabolism -0.04 0.0093143 -4.042023 0.0001 0.0032 -0.06 -0.02
Metabolism..Amino.Acid.Metabolism..Valine..leucine.and.isoleucine.biosynthesis -0.07 0.0177233 -4.024218 0.0001 0.0032 -0.11 -0.04
Metabolism..Amino.Acid.Metabolism..Glycine..serine.and.threonine.metabolism -0.04 0.0094211 -3.892352 0.0001 0.0039 -0.06 -0.02
Environmental.Information.Processing..Membrane.Transport..Phosphotransferase.system..PTS. 0.14 0.0359911 3.886257 0.0001 0.0039 0.07 0.21
Unclassified..Metabolism..Carbohydrate.metabolism -0.10 0.0263032 -3.856911 0.0001 0.0039 -0.15 -0.05
Metabolism..Amino.Acid.Metabolism..Lysine.biosynthesis -0.06 0.0167669 -3.782466 0.0002 0.0046 -0.10 -0.03
Unclassified..Cellular.Processes.and.Signaling..Membrane.and.intracellular.structural.molecules 0.20 0.0539469 3.734553 0.0002 0.0048 0.10 0.31
Metabolism..Amino.Acid.Metabolism..Tyrosine.metabolism 0.04 0.0100122 3.717164 0.0002 0.0048 0.02 0.06
Metabolism..Glycan.Biosynthesis.and.Metabolism..Lipopolysaccharide.biosynthesis.proteins 0.29 0.0793759 3.682344 0.0003 0.0050 0.14 0.45
Unclassified..Cellular.Processes.and.Signaling..Pores.ion.channels 0.21 0.0597116 3.549333 0.0004 0.0074 0.09 0.33
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Thiamine.metabolism -0.05 0.0154782 -3.535522 0.0005 0.0074 -0.09 -0.02
Environmental.Information.Processing..Membrane.Transport..Transporters -0.05 0.0148166 -3.511500 0.0005 0.0076 -0.08 -0.02
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Chloroalkane.and.chloroalkene.degradation -0.07 0.0210568 -3.471330 0.0006 0.0079 -0.11 -0.03
Environmental.Information.Processing..Membrane.Transport..Secretion.system 0.13 0.0378618 3.465041 0.0006 0.0079 0.06 0.21
Unclassified..Metabolism..Energy.metabolism 0.13 0.0390210 3.449100 0.0006 0.0079 0.06 0.21
Metabolism..Glycan.Biosynthesis.and.Metabolism..Glycosyltransferases 0.16 0.0475128 3.431370 0.0007 0.0080 0.07 0.26
Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.09 0.0257143 -3.417511 0.0007 0.0080 -0.14 -0.04
Organismal.Systems..Endocrine.System..PPAR.signaling.pathway -0.14 0.0429330 -3.373723 0.0008 0.0089 -0.23 -0.06
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.08 0.0248050 3.337006 0.0010 0.0096 0.03 0.13
Metabolism..Amino.Acid.Metabolism..Cysteine.and.methionine.metabolism -0.04 0.0134748 -3.305994 0.0011 0.0098 -0.07 -0.02
Unclassified..Cellular.Processes.and.Signaling..Cell.motility.and.secretion 0.09 0.0285829 3.304863 0.0011 0.0098 0.04 0.15
Metabolism..Carbohydrate.Metabolism..Starch.and.sucrose.metabolism -0.08 0.0236972 -3.287954 0.0011 0.0098 -0.12 -0.03
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Riboflavin.metabolism 0.10 0.0296068 3.282614 0.0011 0.0098 0.04 0.16
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Sulfur.relay.system 0.14 0.0439438 3.263629 0.0012 0.0098 0.06 0.23
Organismal.Systems..Endocrine.System..Adipocytokine.signaling.pathway -0.18 0.0548935 -3.260450 0.0012 0.0098 -0.29 -0.07
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Nicotinate.and.nicotinamide.metabolism -0.06 0.0193088 -3.218336 0.0014 0.0109 -0.10 -0.02
Unclassified..Cellular.Processes.and.Signaling..Other.transporters 0.12 0.0385481 3.180404 0.0016 0.0118 0.05 0.20
Metabolism..Carbohydrate.Metabolism..Butanoate.metabolism 0.05 0.0166437 3.174645 0.0017 0.0118 0.02 0.09
Metabolism..Lipid.Metabolism..Glycerophospholipid.metabolism 0.05 0.0166210 3.138757 0.0019 0.0129 0.02 0.08
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Xylene.degradation -0.06 0.0197940 -3.102301 0.0021 0.0140 -0.10 -0.02
Genetic.Information.Processing..Folding..Sorting.and.Degradation..RNA.degradation -0.04 0.0142902 -3.082891 0.0022 0.0140 -0.07 -0.02
Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Phenylpropanoid.biosynthesis -0.13 0.0410567 -3.083039 0.0022 0.0140 -0.21 -0.05
Metabolism..Carbohydrate.Metabolism..Propanoate.metabolism 0.04 0.0124717 3.066496 0.0024 0.0140 0.01 0.06
Unclassified..Poorly.Characterized..General.function.prediction.only 0.02 0.0058957 3.062192 0.0024 0.0140 0.01 0.03
Genetic.Information.Processing..Replication.and.Repair..Nucleotide.excision.repair -0.09 0.0283217 -3.061088 0.0024 0.0140 -0.14 -0.03
Environmental.Information.Processing..Signal.Transduction..Two.component.system 0.14 0.0467257 3.051950 0.0025 0.0140 0.05 0.23
Unclassified..Metabolism..Amino.acid.metabolism 0.13 0.0418094 3.042619 0.0026 0.0141 0.05 0.21
Metabolism..Lipid.Metabolism..Lipid.biosynthesis.proteins 0.01 0.0048136 3.030041 0.0027 0.0143 0.01 0.02
Genetic.Information.Processing..Transcription..Transcription.factors 0.04 0.0134457 2.997917 0.0029 0.0155 0.01 0.07
Metabolism..Metabolism.of.Other.Amino.Acids..beta.Alanine.metabolism 0.17 0.0579307 2.979703 0.0031 0.0160 0.06 0.29
Environmental.Information.Processing..Signaling.Molecules.and.Interaction..Bacterial.toxins -0.14 0.0467118 -2.949014 0.0034 0.0173 -0.23 -0.05
Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.08 0.0285967 -2.925386 0.0037 0.0178 -0.14 -0.03
Organismal.Systems..Nervous.System..Glutamatergic.synapse -0.06 0.0221222 -2.923405 0.0037 0.0178 -0.11 -0.02
Metabolism..Lipid.Metabolism..Fatty.acid.biosynthesis 0.08 0.0284438 2.919096 0.0038 0.0178 0.03 0.14
Unclassified..Poorly.Characterized..Function.unknown 0.06 0.0198184 2.909409 0.0039 0.0179 0.02 0.10
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Aminobenzoate.degradation 0.13 0.0458266 2.888243 0.0042 0.0188 0.04 0.22
Unclassified..Metabolism..Metabolism.of.cofactors.and.vitamins 0.14 0.0473071 2.877498 0.0043 0.0189 0.04 0.23
Metabolism..Glycan.Biosynthesis.and.Metabolism..Other.glycan.degradation -0.15 0.0540601 -2.860084 0.0045 0.0197 -0.26 -0.05
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Limonene.and.pinene.degradation 0.13 0.0453014 2.842982 0.0048 0.0200 0.04 0.22
Environmental.Information.Processing..Membrane.Transport..Bacterial.secretion.system 0.07 0.0232601 2.841100 0.0048 0.0200 0.02 0.11
Cellular.Processes..Cell.Motility..Flagellar.assembly 0.32 0.1157154 2.796610 0.0055 0.0225 0.10 0.55
Metabolism..Carbohydrate.Metabolism..Glyoxylate.and.dicarboxylate.metabolism 0.06 0.0231906 2.766731 0.0060 0.0242 0.02 0.11
Metabolism..Lipid.Metabolism..Glycerolipid.metabolism 0.06 0.0220342 2.728753 0.0067 0.0266 0.02 0.10
Metabolism..Amino.Acid.Metabolism..Alanine..aspartate.and.glutamate.metabolism -0.04 0.0136838 -2.707962 0.0072 0.0278 -0.06 -0.01
Metabolism..Amino.Acid.Metabolism..Valine..leucine.and.isoleucine.degradation 0.07 0.0261697 2.694539 0.0074 0.0283 0.02 0.12
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.04 0.0133974 -2.678519 0.0078 0.0287 -0.06 -0.01
Metabolism..Energy.Metabolism..Carbon.fixation.pathways.in.prokaryotes 0.02 0.0080459 2.677095 0.0078 0.0287 0.01 0.04
Metabolism..Glycan.Biosynthesis.and.Metabolism..Lipopolysaccharide.biosynthesis 0.31 0.1169356 2.672866 0.0079 0.0287 0.08 0.54
Unclassified..Cellular.Processes.and.Signaling..Other.ion.coupled.transporters 0.05 0.0188592 2.649877 0.0085 0.0302 0.01 0.09
Metabolism..Energy.Metabolism..Photosynthesis.proteins -0.05 0.0198840 -2.632856 0.0089 0.0312 -0.09 -0.01
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Proteasome -0.16 0.0623648 -2.617364 0.0093 0.0322 -0.29 -0.04
Metabolism..Metabolism.of.Other.Amino.Acids..Selenocompound.metabolism -0.03 0.0122327 -2.597275 0.0099 0.0335 -0.06 -0.01
Metabolism..Energy.Metabolism..Photosynthesis -0.06 0.0219419 -2.584462 0.0102 0.0342 -0.10 -0.01
Cellular.Processes..Cell.Motility..Cytoskeleton.proteins -0.06 0.0231623 -2.571828 0.0106 0.0350 -0.10 -0.01
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Prenyltransferases -0.04 0.0166380 -2.553962 0.0111 0.0361 -0.08 -0.01
Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Novobiocin.biosynthesis -0.03 0.0126197 -2.550160 0.0113 0.0361 -0.06 -0.01
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Benzoate.degradation 0.08 0.0327414 2.541543 0.0115 0.0364 0.02 0.15
Metabolism..Carbohydrate.Metabolism..Citrate.cycle..TCA.cycle. 0.03 0.0126634 2.490534 0.0133 0.0413 0.01 0.06
Cellular.Processes..Cell.Motility..Bacterial.motility.proteins 0.19 0.0776254 2.478104 0.0137 0.0422 0.04 0.34
Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.05 0.0185272 -2.464623 0.0143 0.0432 -0.08 -0.01
Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.04 0.0147013 2.446898 0.0150 0.0447 0.01 0.06
Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Streptomycin.biosynthesis -0.05 0.0207643 -2.442434 0.0152 0.0447 -0.09 -0.01
Genetic.Information.Processing..Replication.and.Repair..DNA.repair.and.recombination.proteins -0.03 0.0115746 -2.437363 0.0154 0.0447 -0.05 -0.01
Genetic.Information.Processing..Replication.and.Repair..Homologous.recombination -0.04 0.0162049 -2.422491 0.0160 0.0459 -0.07 -0.01
Metabolism..Lipid.Metabolism..Sphingolipid.metabolism -0.12 0.0495204 -2.370620 0.0184 0.0521 -0.21 -0.02
Unclassified..Metabolism..Others 0.03 0.0109240 2.335657 0.0202 0.0560 0.00 0.05
Genetic.Information.Processing..Translation..Aminoacyl.tRNA.biosynthesis -0.05 0.0219340 -2.333591 0.0203 0.0560 -0.09 -0.01
Environmental.Information.Processing..Membrane.Transport..ABC.transporters -0.02 0.0098570 -2.298590 0.0222 0.0600 -0.04 0.00
Metabolism..Energy.Metabolism..Methane.metabolism -0.02 0.0070473 -2.297401 0.0223 0.0600 -0.03 0.00
Metabolism..Carbohydrate.Metabolism..Glycolysis…Gluconeogenesis -0.03 0.0114624 -2.291432 0.0226 0.0601 -0.05 0.00
Unclassified..Cellular.Processes.and.Signaling..Signal.transduction.mechanisms 0.03 0.0114439 2.287667 0.0229 0.0601 0.00 0.05
Environmental.Information.Processing..Signal.Transduction..Phosphatidylinositol.signaling.system 0.02 0.0094755 2.268460 0.0240 0.0624 0.00 0.04
Genetic.Information.Processing..Translation..Ribosome -0.05 0.0213387 -2.261201 0.0244 0.0628 -0.09 -0.01
Metabolism..Amino.Acid.Metabolism..Lysine.degradation 0.13 0.0583100 2.228455 0.0266 0.0675 0.02 0.24
Metabolism..Amino.Acid.Metabolism..Tryptophan.metabolism 0.09 0.0405700 2.217799 0.0273 0.0686 0.01 0.17
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.07 0.0299017 2.213026 0.0277 0.0687 0.01 0.12
Metabolism..Carbohydrate.Metabolism..Pyruvate.metabolism 0.02 0.0094877 2.161076 0.0315 0.0773 0.00 0.04
Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Terpenoid.backbone.biosynthesis -0.04 0.0168638 -2.154288 0.0320 0.0777 -0.07 0.00
Metabolism..Lipid.Metabolism..Secondary.bile.acid.biosynthesis -0.15 0.0699055 -2.138006 0.0333 0.0794 -0.29 -0.01
Metabolism..Lipid.Metabolism..Primary.bile.acid.biosynthesis -0.15 0.0697841 -2.137277 0.0334 0.0794 -0.29 -0.01
Metabolism..Metabolism.of.Other.Amino.Acids..Glutathione.metabolism 0.03 0.0160273 2.125443 0.0343 0.0806 0.00 0.07
Metabolism..Carbohydrate.Metabolism..Galactose.metabolism -0.05 0.0237979 -2.121521 0.0347 0.0806 -0.10 0.00
Metabolism..Metabolism.of.Other.Amino.Acids..D.Glutamine.and.D.glutamate.metabolism -0.03 0.0145028 -2.099477 0.0366 0.0842 -0.06 0.00
Genetic.Information.Processing..Transcription..Transcription.machinery -0.02 0.0110271 -2.091515 0.0373 0.0850 -0.04 0.00
Unclassified..Genetic.Information.Processing..Restriction.enzyme -0.08 0.0394060 -2.072812 0.0390 0.0880 -0.16 0.00
Metabolism..Enzyme.Families..Peptidases -0.02 0.0079776 -2.044205 0.0418 0.0927 -0.03 0.00
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Biotin.metabolism 0.08 0.0396205 2.042768 0.0419 0.0927 0.00 0.16
Unclassified..Cellular.Processes.and.Signaling..Sporulation -0.15 0.0738199 -2.000512 0.0463 0.1014 -0.29 0.00

Meta-analysis on 4 studies with gender info but adjusting for age only (no gender)

Alpha diversity

Shannon

                                           RD            95%-CI %W(fixed)
Subramanian et al 2014 ( Bangladesh )  0.2592 [ 0.1185; 0.3999]      76.8
Bender et al 2016 ( Haiti )           -0.1146 [-0.7954; 0.5662]       3.3
Pannaraj et al 2017 ( USA(CA_FL) )     0.3732 [ 0.0808; 0.6657]      17.8
Thompson et al 2015 ( USA(NC) )        0.3001 [-0.5308; 1.1310]       2.2
                                      %W(random)
Subramanian et al 2014 ( Bangladesh )       76.8
Bender et al 2016 ( Haiti )                  3.3
Pannaraj et al 2017 ( USA(CA_FL) )          17.8
Thompson et al 2015 ( USA(NC) )              2.2

Number of studies combined: k = 4

                         RD           95%-CI    z  p-value
Fixed effect model   0.2681 [0.1448; 0.3914] 4.26 < 0.0001
Random effects model 0.2681 [0.1448; 0.3914] 4.26 < 0.0001

Quantifying heterogeneity:
tau^2 = 0; H = 1.00 [1.00; 1.94]; I^2 = 0.0% [0.0%; 73.5%]

Test of heterogeneity:
    Q d.f. p-value
 1.73    3  0.6300

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 ( Bangladesh ) 0.000305463231694058
Bender et al 2016 ( Haiti ) 0.74142212926805
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0123688713005407
Thompson et al 2015 ( USA(NC) ) 0.479014124949741

Other indexes

Microbiota age

                                           RD            95%-CI %W(fixed)
Thompson et al 2015 ( USA(NC) )        0.8754 [ 0.1366; 1.6142]       1.9
Pannaraj et al 2017 ( USA(CA_FL) )     0.2665 [ 0.0464; 0.4866]      21.2
Bender et al 2016 ( Haiti )           -0.1769 [-0.8203; 0.4664]       2.5
Subramanian et al 2014 ( Bangladesh )  0.0568 [-0.0605; 0.1741]      74.5
                                      %W(random)
Thompson et al 2015 ( USA(NC) )              8.9
Pannaraj et al 2017 ( USA(CA_FL) )          35.4
Bender et al 2016 ( Haiti )                 11.1
Subramanian et al 2014 ( Bangladesh )       44.6

Number of studies combined: k = 4

                         RD            95%-CI    z p-value
Fixed effect model   0.1107 [ 0.0095; 0.2120] 2.14  0.0320
Random effects model 0.1778 [-0.0652; 0.4208] 1.43  0.1515

Quantifying heterogeneity:
tau^2 = 0.0309; H = 1.59 [1.00; 2.76]; I^2 = 60.6% [0.0%; 86.8%]

Test of heterogeneity:
    Q d.f. p-value
 7.62    3  0.0546

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Thompson et al 2015 ( USA(NC) ) 0.0202100021212404
Pannaraj et al 2017 ( USA(CA_FL) ) 0.0176451947099079
Bender et al 2016 ( Haiti ) 0.589859305402284
Subramanian et al 2014 ( Bangladesh ) 0.342537683608756

Taxa relative abundance

Phylum (l2)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__bacteroidetes 0.23 0.0929009 0.05 0.41 2.506500 0.0122 0.1097
k__bacteria.p__firmicutes 0.18 0.0865984 0.01 0.35 2.029901 0.0424 0.1906

Order (l4)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__firmicutes.c__bacilli.o__bacillales -0.30 0.0877116 -0.47 -0.12 -3.375411 0.0007 0.0435
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.24 0.0930692 0.05 0.42 2.540047 0.0111 0.1799

Family (l5)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__actinobacteria.c__actinobacteria.o__actinomycetales.f__propionibacteriaceae 10.37 0.0096364 10.35 10.39 1076.462007 0.0000 0.0000
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae 0.34 0.0921764 0.16 0.52 3.729947 0.0002 0.0088
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae -0.34 0.0914966 -0.52 -0.16 -3.708352 0.0002 0.0088
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae 0.27 0.1012548 0.07 0.47 2.644067 0.0082 0.1936
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__carnobacteriaceae -0.32 0.1334885 -0.58 -0.05 -2.363485 0.0181 0.2555

Genus (l6)

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
k__bacteria.p__actinobacteria.c__actinobacteria.o__actinomycetales.f__propionibacteriaceae.g__propionibacterium 10.37 0.0096364 10.35 10.39 1076.462007 0.0000 0.0000
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__acidaminococcus 3.37 0.4299927 2.53 4.21 7.834021 0.0000 0.0000
k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae.g__staphylococcus -0.34 0.0919245 -0.52 -0.16 -3.671411 0.0002 0.0103
k__bacteria.p__proteobacteria.c__betaproteobacteria.o__burkholderiales.f__oxalobacteraceae.g__ralstonia -1.12 0.3911578 -1.89 -0.35 -2.861588 0.0042 0.1349
k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__bacteroidaceae.g__bacteroides 0.27 0.1012548 0.07 0.47 2.644067 0.0082 0.2003
k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__.eubacterium. 0.45 0.1719112 0.11 0.79 2.627310 0.0086 0.2003
k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales.f__carnobacteriaceae.g__granulicatella -0.32 0.1335258 -0.58 -0.05 -2.360386 0.0183 0.2921
k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__veillonella 0.35 0.1530337 0.05 0.65 2.310869 0.0208 0.3138
k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__pseudomonadales.f__pseudomonadaceae.g__pseudomonas -0.26 0.1324610 -0.52 0.00 -1.981408 0.0475 0.5506

KEGG pathway

Level 2

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Glycan.Biosynthesis.and.Metabolism 0.05 0.0122304 0.03 0.08 4.345847 0.0000 0.0005
Genetic.Information.Processing..Transcription 0.02 0.0054094 0.01 0.03 3.056402 0.0022 0.0426
Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.06 0.0207122 -0.10 -0.02 -2.824348 0.0047 0.0600
Genetic.Information.Processing..Folding..Sorting.and.Degradation 0.01 0.0037159 0.00 0.02 2.221199 0.0263 0.2502
Metabolism..Biosynthesis.of.Other.Secondary.Metabolites -0.03 0.0125900 -0.05 0.00 -2.021111 0.0433 0.3288

Level 3 KEGG pathway

estimate.nebf se.nebf ll.nebf ul.nebf z.nebf p.nebf p.adjust.nebf
Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.09 0.0177520 0.05 0.12 4.990180 0.0000 0.0001
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Chaperones.and.folding.catalysts 0.03 0.0071842 0.02 0.05 4.580385 0.0000 0.0005
Environmental.Information.Processing..Membrane.Transport..Phosphotransferase.system..PTS. 0.13 0.0305596 0.07 0.19 4.219569 0.0000 0.0019
Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.06 0.0175651 -0.10 -0.03 -3.631992 0.0003 0.0162
Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Xylene.degradation -0.06 0.0192851 -0.10 -0.02 -2.985966 0.0028 0.1300
Organismal.Systems..Endocrine.System..PPAR.signaling.pathway -0.10 0.0353891 -0.17 -0.03 -2.746360 0.0060 0.2133
Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.07 0.0269951 -0.13 -0.02 -2.721881 0.0065 0.2133
Unclassified..Cellular.Processes.and.Signaling..Signal.transduction.mechanisms 0.02 0.0091880 0.01 0.04 2.534213 0.0113 0.2827
Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.03 0.0118755 0.01 0.05 2.492261 0.0127 0.2827
Unclassified..Cellular.Processes.and.Signaling..Other.ion.coupled.transporters 0.03 0.0124677 0.01 0.06 2.470926 0.0135 0.2827
Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.03 0.0106104 -0.05 -0.01 -2.460078 0.0139 0.2827
Environmental.Information.Processing..Signal.Transduction..Phosphatidylinositol.signaling.system 0.02 0.0088373 0.00 0.04 2.411772 0.0159 0.2827
Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.05 0.0214619 0.01 0.09 2.409349 0.0160 0.2827
Genetic.Information.Processing..Folding..Sorting.and.Degradation..Proteasome -0.11 0.0543425 -0.22 -0.01 -2.104930 0.0353 0.5799

Adjusting for age and gender

Bangladesh data

Alpha diversity

id Estimate.bfNon_exclusiveBF Std. Error.bfNon_exclusiveBF t value.bfNon_exclusiveBF Pr(>|t|).bfNon_exclusiveBF
chao1 0.07 0.04 1.66 0.0961
observed_species 0.07 0.04 1.69 0.0905
pd_whole_tree 0.10 0.04 2.49 0.0127
shannon 0.26 0.07 3.58 0.0003

Microbiota age

Estimate Std. Error df t value Pr(>|t|) varname pop
bfNo_BF -0.1075706 0.1666272 248.75546 -0.6455766 0.5191486 bfNo_BF Bangladesh
bfNon_exclusiveBF 0.0339266 0.0571267 202.03700 0.5938845 0.5532537 bfNon_exclusiveBF Bangladesh
genderMale -0.0909496 0.0595166 36.06456 -1.5281378 0.1352025 genderMale Bangladesh
age.sample 0.0862128 0.0136845 236.02555 6.3000537 0.0000000 age.sample Bangladesh

Taxa relative abundance

phylum

id Estimate.bfNon_exclusiveBF ll ul Pr(>|t|).bfNon_exclusiveBF pval.adjust.bfNon_exclusiveBF
5 k__bacteria.p__proteobacteria 0.37 0.11 0.63 0.0061 0.0448
1 k__bacteria.p__actinobacteria -0.37 -0.64 -0.10 0.0086 0.0590
3 k__bacteria.p__firmicutes 0.24 0.01 0.46 0.0428 0.1767

order

id Estimate.bfNon_exclusiveBF ll ul Pr(>|t|).bfNon_exclusiveBF pval.adjust.bfNon_exclusiveBF
26 k__bacteria.p__proteobacteria.c__epsilonproteobacteria.o__campylobacterales 0.92 0.47 1.36 0.0001 0.0015
28 k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales 0.37 0.11 0.64 0.0057 0.0448
17 k__bacteria.p__actinobacteria.c__actinobacteria.o__bifidobacteriales -0.39 -0.67 -0.12 0.0057 0.0448
22 k__bacteria.p__firmicutes.c__bacilli.o__lactobacillales 0.25 0.01 0.48 0.0380 0.1728
18 k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales 0.27 0.02 0.53 0.0386 0.1728

family

id Estimate.bfNon_exclusiveBF ll ul Pr(>|t|).bfNon_exclusiveBF pval.adjust.bfNon_exclusiveBF
51 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__eubacteriaceae -2.06 -2.95 -1.17 0.0000 0.0005
59 k__bacteria.p__proteobacteria.c__epsilonproteobacteria.o__campylobacterales.f__campylobacteraceae 0.96 0.50 1.41 0.0001 0.0015
61 k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae 0.37 0.11 0.64 0.0057 0.0448
34 k__bacteria.p__actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae -0.39 -0.67 -0.12 0.0057 0.0448
60 k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__aeromonadales.f__aeromonadaceae 1.15 0.22 2.09 0.0159 0.0920
35 k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae 0.27 0.02 0.53 0.0386 0.1728
42 k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae -0.27 -0.52 -0.01 0.0402 0.1728
37 k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales.f__porphyromonadaceae 0.73 0.04 1.43 0.0404 0.1728

genus

id Estimate.bfNon_exclusiveBF ll ul Pr(>|t|).bfNon_exclusiveBF pval.adjust.bfNon_exclusiveBF
93 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__eubacteriaceae.g__pseudoramibacter_eubacterium -2.06 -2.95 -1.17 0.0000 0.0005
116 k__bacteria.p__proteobacteria.c__epsilonproteobacteria.o__campylobacterales.f__campylobacteraceae.g__campylobacter 0.96 0.50 1.41 0.0001 0.0015
78 k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__bacillaceae.g__ 1.28 0.44 2.12 0.0030 0.0448
99 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__.ruminococcus. 0.59 0.18 1.00 0.0050 0.0448
69 k__bacteria.p__actinobacteria.c__actinobacteria.o__bifidobacteriales.f__bifidobacteriaceae.g__bifidobacterium -0.39 -0.67 -0.12 0.0057 0.0448
119 k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__enterobacteriales.f__enterobacteriaceae.g__ 0.37 0.11 0.63 0.0060 0.0448
100 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__peptostreptococcaceae.g__ 0.68 0.17 1.19 0.0092 0.0601
70 k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae.g__ 0.41 0.09 0.73 0.0118 0.0731
117 k__bacteria.p__proteobacteria.c__gammaproteobacteria.o__aeromonadales.f__aeromonadaceae.g__ 1.15 0.22 2.08 0.0163 0.0920
64 k__bacteria.p__actinobacteria.c__actinobacteria.o__actinomycetales.f__actinomycetaceae.g__actinomyces -0.39 -0.73 -0.05 0.0274 0.1477
80 k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae.g__staphylococcus -0.26 -0.52 -0.01 0.0449 0.1795

KEGG pathway

Level 2

id Estimate.bfNon_exclusiveBF ll ul Pr(>|t|).bfNon_exclusiveBF pval.adjust.bfNon_exclusiveBF
16 Metabolism..Glycan.Biosynthesis.and.Metabolism 0.07 0.04 0.10 0.0000 0.0013
1 Metabolism..Amino.Acid.Metabolism -0.04 -0.06 -0.02 0.0002 0.0036
30 Unclassified..Poorly.Characterized 0.03 0.01 0.05 0.0008 0.0083
23 Unclassified..Metabolism 0.07 0.03 0.11 0.0009 0.0083
20 Metabolism..Lipid.Metabolism 0.02 0.01 0.03 0.0016 0.0103
9 Organismal.Systems..Endocrine.System -0.12 -0.19 -0.04 0.0017 0.0103
32 Environmental.Information.Processing..Signal.Transduction 0.12 0.04 0.20 0.0034 0.0177
27 Organismal.Systems..Nervous.System -0.06 -0.11 -0.02 0.0042 0.0177
19 Human.Diseases..Infectious.Diseases 0.05 0.01 0.08 0.0043 0.0177
33 Environmental.Information.Processing..Signaling.Molecules.and.Interaction -0.09 -0.15 -0.03 0.0055 0.0187
36 Cellular.Processes..Transport.and.Catabolism -0.08 -0.13 -0.02 0.0057 0.0187
7 Unclassified..Cellular.Processes.and.Signaling 0.07 0.02 0.13 0.0061 0.0187
34 Genetic.Information.Processing..Transcription 0.02 0.01 0.03 0.0067 0.0192
2 Metabolism..Biosynthesis.of.Other.Secondary.Metabolites -0.04 -0.07 -0.01 0.0117 0.0307
26 Metabolism..Metabolism.of.Terpenoids.and.Polyketides 0.01 0.00 0.02 0.0124 0.0307
25 Metabolism..Metabolism.of.Other.Amino.Acids 0.01 0.00 0.02 0.0145 0.0335
6 Cellular.Processes..Cell.Motility 0.15 0.03 0.27 0.0154 0.0335
28 Human.Diseases..Neurodegenerative.Diseases 0.09 0.02 0.17 0.0174 0.0344
37 Metabolism..Xenobiotics.Biodegradation.and.Metabolism 0.03 0.01 0.06 0.0177 0.0344
31 Genetic.Information.Processing..Replication.and.Repair -0.03 -0.05 0.00 0.0375 0.0693
12 Metabolism..Enzyme.Families -0.01 -0.02 0.00 0.0417 0.0735

Level 3

id Estimate.bfNon_exclusiveBF ll ul Pr(>|t|).bfNon_exclusiveBF pval.adjust.bfNon_exclusiveBF
33 Metabolism..Carbohydrate.Metabolism..C5.Branched.dibasic.acid.metabolism -0.09 -0.13 -0.05 0.0000 0.0038
44 Genetic.Information.Processing..Folding..Sorting.and.Degradation..Chaperones.and.folding.catalysts 0.04 0.02 0.06 0.0001 0.0038
139 Metabolism..Amino.Acid.Metabolism..Phenylalanine..tyrosine.and.tryptophan.biosynthesis -0.08 -0.12 -0.04 0.0001 0.0038
15 Metabolism..Amino.Acid.Metabolism..Arginine.and.proline.metabolism -0.04 -0.06 -0.02 0.0001 0.0038
213 Metabolism..Amino.Acid.Metabolism..Valine..leucine.and.isoleucine.biosynthesis -0.07 -0.11 -0.04 0.0001 0.0040
81 Metabolism..Amino.Acid.Metabolism..Glycine..serine.and.threonine.metabolism -0.04 -0.05 -0.02 0.0001 0.0046
143 Environmental.Information.Processing..Membrane.Transport..Phosphotransferase.system..PTS. 0.14 0.07 0.21 0.0002 0.0046
36 Unclassified..Metabolism..Carbohydrate.metabolism -0.10 -0.15 -0.05 0.0002 0.0046
103 Metabolism..Amino.Acid.Metabolism..Lysine.biosynthesis -0.06 -0.10 -0.03 0.0002 0.0054
108 Unclassified..Cellular.Processes.and.Signaling..Membrane.and.intracellular.structural.molecules 0.20 0.09 0.31 0.0003 0.0058
102 Metabolism..Glycan.Biosynthesis.and.Metabolism..Lipopolysaccharide.biosynthesis.proteins 0.29 0.13 0.45 0.0003 0.0064
210 Metabolism..Amino.Acid.Metabolism..Tyrosine.metabolism 0.04 0.02 0.06 0.0004 0.0069
149 Unclassified..Cellular.Processes.and.Signaling..Pores.ion.channels 0.21 0.09 0.33 0.0005 0.0086
196 Metabolism..Metabolism.of.Cofactors.and.Vitamins..Thiamine.metabolism -0.05 -0.08 -0.02 0.0006 0.0086
203 Environmental.Information.Processing..Membrane.Transport..Transporters -0.05 -0.08 -0.02 0.0007 0.0086
45 Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Chloroalkane.and.chloroalkene.degradation -0.07 -0.11 -0.03 0.0007 0.0086
181 Environmental.Information.Processing..Membrane.Transport..Secretion.system 0.13 0.06 0.20 0.0007 0.0086
61 Unclassified..Metabolism..Energy.metabolism 0.13 0.06 0.21 0.0007 0.0086
86 Metabolism..Glycan.Biosynthesis.and.Metabolism..Glycosyltransferases 0.16 0.07 0.26 0.0007 0.0086
136 Cellular.Processes..Transport.and.Catabolism..Peroxisome -0.09 -0.14 -0.04 0.0009 0.0095
128 Organismal.Systems..Endocrine.System..PPAR.signaling.pathway -0.14 -0.23 -0.06 0.0010 0.0101
70 Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.08 0.03 0.13 0.0012 0.0111
176 Metabolism..Metabolism.of.Cofactors.and.Vitamins..Riboflavin.metabolism 0.10 0.04 0.16 0.0013 0.0111
50 Metabolism..Amino.Acid.Metabolism..Cysteine.and.methionine.metabolism -0.04 -0.07 -0.02 0.0013 0.0111
41 Unclassified..Cellular.Processes.and.Signaling..Cell.motility.and.secretion 0.09 0.04 0.15 0.0013 0.0111
187 Metabolism..Carbohydrate.Metabolism..Starch.and.sucrose.metabolism -0.08 -0.12 -0.03 0.0013 0.0111
191 Genetic.Information.Processing..Folding..Sorting.and.Degradation..Sulfur.relay.system 0.14 0.06 0.23 0.0014 0.0116
2 Organismal.Systems..Endocrine.System..Adipocytokine.signaling.pathway -0.18 -0.28 -0.07 0.0015 0.0116
116 Metabolism..Metabolism.of.Cofactors.and.Vitamins..Nicotinate.and.nicotinamide.metabolism -0.06 -0.10 -0.02 0.0017 0.0127
125 Unclassified..Cellular.Processes.and.Signaling..Other.transporters 0.12 0.05 0.20 0.0019 0.0138
31 Metabolism..Carbohydrate.Metabolism..Butanoate.metabolism 0.05 0.02 0.09 0.0019 0.0138
140 Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Phenylpropanoid.biosynthesis -0.13 -0.21 -0.05 0.0021 0.0145
80 Metabolism..Lipid.Metabolism..Glycerophospholipid.metabolism 0.05 0.02 0.08 0.0022 0.0145
169 Genetic.Information.Processing..Folding..Sorting.and.Degradation..RNA.degradation -0.04 -0.07 -0.02 0.0026 0.0160
217 Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Xylene.degradation -0.06 -0.10 -0.02 0.0027 0.0160
156 Metabolism..Carbohydrate.Metabolism..Propanoate.metabolism 0.04 0.01 0.06 0.0027 0.0160
73 Unclassified..Poorly.Characterized..General.function.prediction.only 0.02 0.01 0.03 0.0028 0.0160
120 Genetic.Information.Processing..Replication.and.Repair..Nucleotide.excision.repair -0.09 -0.14 -0.03 0.0028 0.0160
6 Unclassified..Metabolism..Amino.acid.metabolism 0.13 0.04 0.21 0.0028 0.0160
207 Environmental.Information.Processing..Signal.Transduction..Two.component.system 0.14 0.05 0.23 0.0030 0.0164
98 Metabolism..Lipid.Metabolism..Lipid.biosynthesis.proteins 0.01 0.00 0.02 0.0030 0.0164
198 Genetic.Information.Processing..Transcription..Transcription.factors 0.04 0.01 0.07 0.0034 0.0181
220 Metabolism..Metabolism.of.Other.Amino.Acids..beta.Alanine.metabolism 0.17 0.06 0.29 0.0035 0.0181
21 Environmental.Information.Processing..Signaling.Molecules.and.Interaction..Bacterial.toxins -0.14 -0.23 -0.04 0.0039 0.0197
76 Organismal.Systems..Nervous.System..Glutamatergic.synapse -0.06 -0.11 -0.02 0.0042 0.0201
179 Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.08 -0.14 -0.03 0.0042 0.0201
65 Metabolism..Lipid.Metabolism..Fatty.acid.biosynthesis 0.08 0.03 0.14 0.0043 0.0201
71 Unclassified..Poorly.Characterized..Function.unknown 0.06 0.02 0.10 0.0047 0.0211
123 Metabolism..Glycan.Biosynthesis.and.Metabolism..Other.glycan.degradation -0.15 -0.26 -0.05 0.0047 0.0211
10 Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Aminobenzoate.degradation 0.13 0.04 0.22 0.0048 0.0211
109 Unclassified..Metabolism..Metabolism.of.cofactors.and.vitamins 0.13 0.04 0.23 0.0052 0.0226
96 Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Limonene.and.pinene.degradation 0.13 0.04 0.22 0.0056 0.0236
20 Environmental.Information.Processing..Membrane.Transport..Bacterial.secretion.system 0.07 0.02 0.11 0.0057 0.0238
67 Cellular.Processes..Cell.Motility..Flagellar.assembly 0.32 0.09 0.55 0.0061 0.0248
87 Metabolism..Carbohydrate.Metabolism..Glyoxylate.and.dicarboxylate.metabolism 0.06 0.02 0.11 0.0067 0.0269
79 Metabolism..Lipid.Metabolism..Glycerolipid.metabolism 0.06 0.02 0.10 0.0077 0.0304
4 Metabolism..Amino.Acid.Metabolism..Alanine..aspartate.and.glutamate.metabolism -0.04 -0.06 -0.01 0.0081 0.0307
214 Metabolism..Amino.Acid.Metabolism..Valine..leucine.and.isoleucine.degradation 0.07 0.02 0.12 0.0083 0.0307
101 Metabolism..Glycan.Biosynthesis.and.Metabolism..Lipopolysaccharide.biosynthesis 0.31 0.08 0.54 0.0083 0.0307
38 Metabolism..Energy.Metabolism..Carbon.fixation.pathways.in.prokaryotes 0.02 0.01 0.04 0.0083 0.0307
216 Metabolism..Metabolism.of.Cofactors.and.Vitamins..Vitamin.B6.metabolism -0.04 -0.06 -0.01 0.0091 0.0329
158 Genetic.Information.Processing..Folding..Sorting.and.Degradation..Proteasome -0.16 -0.29 -0.04 0.0098 0.0349
124 Unclassified..Cellular.Processes.and.Signaling..Other.ion.coupled.transporters 0.05 0.01 0.09 0.0101 0.0355
145 Metabolism..Energy.Metabolism..Photosynthesis.proteins -0.05 -0.09 -0.01 0.0105 0.0361
182 Metabolism..Metabolism.of.Other.Amino.Acids..Selenocompound.metabolism -0.03 -0.06 -0.01 0.0112 0.0380
144 Metabolism..Energy.Metabolism..Photosynthesis -0.06 -0.10 -0.01 0.0119 0.0397
51 Cellular.Processes..Cell.Motility..Cytoskeleton.proteins -0.06 -0.10 -0.01 0.0120 0.0397
151 Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Prenyltransferases -0.04 -0.07 -0.01 0.0126 0.0408
23 Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Benzoate.degradation 0.08 0.02 0.15 0.0128 0.0408
119 Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Novobiocin.biosynthesis -0.03 -0.06 -0.01 0.0129 0.0408
48 Metabolism..Carbohydrate.Metabolism..Citrate.cycle..TCA.cycle. 0.03 0.01 0.06 0.0141 0.0440
19 Cellular.Processes..Cell.Motility..Bacterial.motility.proteins 0.19 0.04 0.34 0.0160 0.0487
52 Metabolism..Metabolism.of.Other.Amino.Acids..D.Alanine.metabolism 0.04 0.01 0.06 0.0161 0.0487
66 Metabolism..Lipid.Metabolism..Fatty.acid.metabolism -0.04 -0.08 -0.01 0.0171 0.0505
188 Metabolism..Biosynthesis.of.Other.Secondary.Metabolites..Streptomycin.biosynthesis -0.05 -0.09 -0.01 0.0172 0.0505
54 Genetic.Information.Processing..Replication.and.Repair..DNA.repair.and.recombination.proteins -0.03 -0.05 0.00 0.0177 0.0514
89 Genetic.Information.Processing..Replication.and.Repair..Homologous.recombination -0.04 -0.07 -0.01 0.0183 0.0526
184 Metabolism..Lipid.Metabolism..Sphingolipid.metabolism -0.12 -0.21 -0.02 0.0198 0.0560
9 Genetic.Information.Processing..Translation..Aminoacyl.tRNA.biosynthesis -0.05 -0.09 -0.01 0.0233 0.0651
126 Unclassified..Metabolism..Others 0.02 0.00 0.05 0.0236 0.0651
111 Metabolism..Energy.Metabolism..Methane.metabolism -0.02 -0.03 0.00 0.0246 0.0672
183 Unclassified..Cellular.Processes.and.Signaling..Signal.transduction.mechanisms 0.03 0.00 0.05 0.0258 0.0694
82 Metabolism..Carbohydrate.Metabolism..Glycolysis…Gluconeogenesis -0.03 -0.05 0.00 0.0261 0.0694
177 Genetic.Information.Processing..Translation..Ribosome -0.05 -0.09 -0.01 0.0280 0.0730
141 Environmental.Information.Processing..Signal.Transduction..Phosphatidylinositol.signaling.system 0.02 0.00 0.04 0.0281 0.0730
1 Environmental.Information.Processing..Membrane.Transport..ABC.transporters -0.02 -0.04 0.00 0.0292 0.0748
104 Metabolism..Amino.Acid.Metabolism..Lysine.degradation 0.13 0.01 0.24 0.0297 0.0748
132 Metabolism..Carbohydrate.Metabolism..Pentose.and.glucuronate.interconversions 0.07 0.01 0.12 0.0298 0.0748
205 Metabolism..Amino.Acid.Metabolism..Tryptophan.metabolism 0.09 0.01 0.17 0.0306 0.0760
167 Metabolism..Carbohydrate.Metabolism..Pyruvate.metabolism 0.02 0.00 0.04 0.0350 0.0851
180 Metabolism..Lipid.Metabolism..Secondary.bile.acid.biosynthesis -0.15 -0.29 -0.01 0.0354 0.0851
152 Metabolism..Lipid.Metabolism..Primary.bile.acid.biosynthesis -0.15 -0.28 -0.01 0.0354 0.0851
194 Metabolism..Metabolism.of.Terpenoids.and.Polyketides..Terpenoid.backbone.biosynthesis -0.04 -0.07 0.00 0.0358 0.0851
72 Metabolism..Carbohydrate.Metabolism..Galactose.metabolism -0.05 -0.10 0.00 0.0389 0.0906
199 Genetic.Information.Processing..Transcription..Transcription.machinery -0.02 -0.04 0.00 0.0390 0.0906
77 Metabolism..Metabolism.of.Other.Amino.Acids..Glutathione.metabolism 0.03 0.00 0.06 0.0397 0.0914
53 Metabolism..Metabolism.of.Other.Amino.Acids..D.Glutamine.and.D.glutamate.metabolism -0.03 -0.06 0.00 0.0406 0.0926
174 Unclassified..Genetic.Information.Processing..Restriction.enzyme -0.08 -0.16 0.00 0.0446 0.1003
29 Metabolism..Metabolism.of.Cofactors.and.Vitamins..Biotin.metabolism 0.08 0.00 0.16 0.0449 0.1003
134 Metabolism..Enzyme.Families..Peptidases -0.02 -0.03 0.00 0.0459 0.1013
185 Unclassified..Cellular.Processes.and.Signaling..Sporulation -0.15 -0.29 0.00 0.0472 0.1034

Meta-analysis of 4 studies with gender info

Alpha diversity

                RD            95%-CI %W(fixed) %W(random)
Bangladesh  0.2582 [ 0.1168; 0.3996]      78.0       78.0
Haiti      -0.1128 [-0.8117; 0.5861]       3.2        3.2
USA(CA_FL)  0.3297 [ 0.0264; 0.6331]      17.0       17.0
USA(UNC)    0.2898 [-0.6376; 1.2172]       1.8        1.8

Number of studies combined: k = 4

                         RD           95%-CI    z  p-value
Fixed effect model   0.2591 [0.1342; 0.3840] 4.07 < 0.0001
Random effects model 0.2591 [0.1342; 0.3840] 4.07 < 0.0001

Quantifying heterogeneity:
tau^2 = 0; H = 1.00 [1.00; 1.68]; I^2 = 0.0% [0.0%; 64.7%]

Test of heterogeneity:
    Q d.f. p-value
 1.30    3  0.7291

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Bangladesh 0.000344378476206655
Haiti 0.751832160135333
USA(CA_FL) 0.033139645082754
USA(UNC) 0.540228852041577

Other indexes

Microbiota age

                                         RD            95%-CI %W(fixed)
Subramanian et al 2014 (Bangladesh)  0.0466 [-0.0707; 0.1639]      74.1
Bender et al 2016 (Haiti)           -0.3112 [-0.9449; 0.3224]       2.5
Pannaraj et al 2017 (USA(CA_FL))     0.2476 [ 0.0253; 0.4699]      20.6
Thompson et al 2015 (USA(NC))        1.0076 [ 0.3937; 1.6215]       2.7
                                    %W(random)
Subramanian et al 2014 (Bangladesh)       37.3
Bender et al 2016 (Haiti)                 14.7
Pannaraj et al 2017 (USA(CA_FL))          32.7
Thompson et al 2015 (USA(NC))             15.3

Number of studies combined: k = 4

                         RD            95%-CI    z p-value
Fixed effect model   0.1050 [ 0.0040; 0.2060] 2.04  0.0416
Random effects model 0.2066 [-0.1000; 0.5133] 1.32  0.1865

Quantifying heterogeneity:
tau^2 = 0.0620; H = 2.04 [1.23; 3.39]; I^2 = 76.0% [33.9%; 91.3%]

Test of heterogeneity:
     Q d.f. p-value
 12.50    3  0.0059

Details on meta-analytical method:
- Inverse variance method
- DerSimonian-Laird estimator for tau^2
study pval
Subramanian et al 2014 (Bangladesh) 0.436137583408132
Bender et al 2016 (Haiti) 0.335677203059515
Pannaraj et al 2017 (USA(CA_FL)) 0.0290537069289293
Thompson et al 2015 (USA(NC)) 0.00129477371396216

Taxa relative abundance

phylum

id estimate ll ul p p.adjust
2 k__bacteria.p__bacteroidetes 0.25 0.05 0.45 0.0123 0.3952
3 k__bacteria.p__firmicutes 0.18 0.01 0.35 0.0399 0.4183

order

id estimate ll ul p p.adjust
24 k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales 0.31 0.06 0.56 0.0150 0.3952
19 k__bacteria.p__bacteroidetes.c__bacteroidia.o__bacteroidales 0.24 0.04 0.43 0.0184 0.3952
18 k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales 0.22 0.02 0.42 0.0310 0.3963
20 k__bacteria.p__firmicutes.c__bacilli.o__bacillales -0.19 -0.37 -0.02 0.0328 0.3963

family

id estimate ll ul p p.adjust
54 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae 0.25 0.06 0.43 0.0080 0.3952
56 k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae 0.31 0.06 0.56 0.0150 0.3952
42 k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae -0.23 -0.43 -0.03 0.0226 0.3952
35 k__bacteria.p__actinobacteria.c__coriobacteriia.o__coriobacteriales.f__coriobacteriaceae 0.22 0.02 0.42 0.0310 0.3963

genus

id estimate ll ul p p.adjust
167 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__acidaminococcus 2.89 1.68 4.10 0.0000 0.0005
102 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__veillonellaceae.g__veillonella 0.22 0.03 0.41 0.0208 0.3952
77 k__bacteria.p__firmicutes.c__bacilli.o__bacillales.f__staphylococcaceae.g__staphylococcus -0.23 -0.43 -0.03 0.0235 0.3952
93 k__bacteria.p__firmicutes.c__clostridia.o__clostridiales.f__lachnospiraceae.g__.ruminococcus. 0.31 0.02 0.61 0.0343 0.3963
106 k__bacteria.p__firmicutes.c__erysipelotrichi.o__erysipelotrichales.f__erysipelotrichaceae.g__ 0.31 0.01 0.61 0.0407 0.4183

KEGG pathway

Level 2

id estimate ll ul p p.adjust
34 Genetic.Information.Processing..Transcription 0.02 0.01 0.03 0.0045 0.1723

Level 3

id estimate ll ul p p.adjust
143 Environmental.Information.Processing..Membrane.Transport..Phosphotransferase.system..PTS. 0.13 0.07 0.19 0.0000 0.0108
217 Metabolism..Xenobiotics.Biodegradation.and.Metabolism..Xylene.degradation -0.06 -0.10 -0.02 0.0029 0.3354
179 Genetic.Information.Processing..Translation..Ribosome.biogenesis.in.eukaryotes -0.07 -0.13 -0.02 0.0068 0.3635
70 Metabolism..Carbohydrate.Metabolism..Fructose.and.mannose.metabolism 0.10 0.03 0.18 0.0079 0.3635
198 Genetic.Information.Processing..Transcription..Transcription.factors 0.03 0.01 0.06 0.0079 0.3635
141 Environmental.Information.Processing..Signal.Transduction..Phosphatidylinositol.signaling.system 0.02 0.00 0.04 0.0171 0.6543
158 Genetic.Information.Processing..Folding..Sorting.and.Degradation..Proteasome -0.12 -0.23 -0.01 0.0274 0.8997
183 Unclassified..Cellular.Processes.and.Signaling..Signal.transduction.mechanisms 0.02 0.00 0.04 0.0367 0.9981
1 Environmental.Information.Processing..Membrane.Transport..ABC.transporters -0.02 -0.04 0.00 0.0402 0.9981

CLR transformation: Performance of the Random Forest model to estimate microbiota age

R session information

R version 3.4.2 (2017-09-28)
Platform: x86_64-w64-mingw32/x64 (64-bit)
Running under: Windows 7 x64 (build 7601) Service Pack 1

Matrix products: default

locale:
[1] LC_COLLATE=English_United States.1252 
[2] LC_CTYPE=English_United States.1252   
[3] LC_MONETARY=English_United States.1252
[4] LC_NUMERIC=C                          
[5] LC_TIME=English_United States.1252    

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] metamicrobiomeR_1.0 devtools_1.13.5     gplots_3.0.1       
 [4] bindrcpp_0.2.2      meta_4.9-2          randomForest_4.6-14
 [7] gdata_2.18.0        scales_0.5.0        wesanderson_0.3.6  
[10] RColorBrewer_1.1-2  geepack_1.2-1       zoo_1.8-0          
[13] itsadug_2.3         plotfunctions_1.3   mgcv_1.8-22        
[16] nlme_3.1-131        reshape2_1.4.3      lmerTest_3.0-1     
[19] sjPlot_2.4.0        sjmisc_2.6.3        lme4_1.1-17        
[22] Matrix_1.2-12       tidyr_0.7.2         dtplyr_0.0.2       
[25] data.table_1.10.4-3 dplyr_0.7.6         date_1.2-37        
[28] lubridate_1.7.1     chron_2.3-51        gmodels_2.16.2     
[31] gridExtra_2.3       plyr_1.8.4          digest_0.6.12      
[34] caret_6.0-80        ggplot2_2.2.1       lattice_0.20-35    
[37] knitr_1.20         

loaded via a namespace (and not attached):
  [1] backports_1.1.1    blme_1.0-4         lazyeval_0.2.1    
  [4] TMB_1.7.11         splines_3.4.2      TH.data_1.0-8     
  [7] foreach_1.4.3      htmltools_0.3.6    memoise_1.1.0     
 [10] magrittr_1.5       sfsmisc_1.1-1      recipes_0.1.1     
 [13] modelr_0.1.1       gower_0.1.2        dimRed_0.1.0      
 [16] sandwich_2.4-0     colorspace_1.3-2   haven_1.1.0       
 [19] crayon_1.3.4       bindr_0.1.1        survival_2.41-3   
 [22] iterators_1.0.8    glue_1.2.0         DRR_0.0.2         
 [25] gtable_0.2.0       ipred_0.9-6        sjstats_0.13.0    
 [28] kernlab_0.9-25     ddalpha_1.3.1      DEoptimR_1.0-8    
 [31] abind_1.4-5        mvtnorm_1.0-6      ggeffects_0.3.0   
 [34] Rcpp_0.12.17       xtable_1.8-2       merTools_0.3.0    
 [37] foreign_0.8-69     stats4_3.4.2       prediction_0.2.0  
 [40] lava_1.5.1         survey_3.32-1      prodlim_1.6.1     
 [43] DT_0.2             httr_1.3.1         htmlwidgets_0.9   
 [46] modeltools_0.2-21  pkgconfig_2.0.1    nnet_7.3-12       
 [49] tidyselect_0.2.3   labeling_0.3       rlang_0.2.1       
 [52] munsell_0.4.3      tools_3.4.2        cli_1.0.0         
 [55] sjlabelled_1.0.5   broom_0.4.3        evaluate_0.10.1   
 [58] stringr_1.2.0      arm_1.9-3          yaml_2.1.15       
 [61] ModelMetrics_1.1.0 robustbase_0.92-8  caTools_1.17.1    
 [64] purrr_0.2.4        coin_1.2-2         mime_0.5          
 [67] RcppRoll_0.2.2     compiler_3.4.2     bayesplot_1.4.0   
 [70] curl_3.0           tibble_1.3.4       stringi_1.1.6     
 [73] highr_0.6          forcats_0.2.0      psych_1.7.8       
 [76] nloptr_1.0.4       effects_4.0-0      stringdist_0.9.4.6
 [79] pwr_1.2-1          lmtest_0.9-35      bitops_1.0-6      
 [82] httpuv_1.3.5       R6_2.2.2           KernSmooth_2.23-15
 [85] codetools_0.2-15   MASS_7.3-47        gtools_3.5.0      
 [88] assertthat_0.2.0   CVST_0.2-1         rprojroot_1.2     
 [91] withr_2.1.0        mnormt_1.5-5       multcomp_1.4-8    
 [94] parallel_3.4.2     grid_3.4.2         rpart_4.1-11      
 [97] timeDate_3042.101  coda_0.19-1        glmmTMB_0.2.0     
[100] class_7.3-14       minqa_1.2.4        rmarkdown_1.10    
[103] snakecase_0.5.1    carData_3.0-0      git2r_0.19.0      
[106] numDeriv_2016.8-1  shiny_1.0.5